Disorders such as schizophrenia and bipolar disorder can significantly impair mood, cognition, and behavior.⁶ These mental illnesses can often be accompanied by comorbidities such as depression and substance abuse, and can significantly impact the quality of life of patients and caregivers.⁶ Luckily, several treatment options for psychotic disorders have been introduced to market since the realization of chlorpromazine's antipsychotic properties in 1952.⁶

Second generation antipsychotics (commonly referred to as atypical antipsychotics) include clozapine, quetiapine, olanzapine, aripiprazole and ziprasidone among others, and are generally thought to be as efficacious as first generation antipsychotics but differ in their adverse effect profiles.^6,7 First generation antipsychotics are associated with extrapyramidal adverse effects while atypical antipsychotics are linked to weight gain, impaired glucose tolerance and metabolic syndrome.^7,8

Ziprasidone is used to treat schizophrenia and bipolar disorder.⁵ It can effectively reduce the rate and time of relapses in schizophrenia, and can be used to treat manic episodes in bipolar disorder although the mechanism of action is unknown.⁵ Although ziprasidone is classified as an atypical antipsychotic, it appears to have a lower incidence of metabolic adverse effects compared to other medications in the same class.⁶

Structure

Similar Structures

Synonyms

Ziprasidona
Ziprasidone
Ziprasidonum

External IDs

CP 88059

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Ziprasidone hydrochloride	JAL53626GG	122883-93-6	NZDBKBRIBJLNNT-UHFFFAOYSA-N
Ziprasidone mesylate trihydrate	3X6SAX83JZ	199191-69-0	WLQZEFFFIUHSJB-UHFFFAOYSA-N

Product Images

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Geodon	Capsule	20 mg/1	Oral	Lake Erie Medical Dba Quality Care Produts Llc	2010-11-05	2018-04-19
Geodon	Capsule	80 mg/1	Oral	Roerig	2001-02-05	Not applicable
Geodon	Capsule	20 mg/1	Oral	Rebel Distributors	2001-02-05	Not applicable
Geodon	Injection, powder, lyophilized, for solution	20 mg/1mL	Intramuscular	Roerig	2017-07-24	Not applicable
Geodon	Injection, powder, lyophilized, for solution	20 mg/1mL	Intramuscular	Cardinal Health	2003-12-23	2014-01-31
Geodon	Capsule	20 mg/1	Oral	Stat Rx USA	2001-02-05	Not applicable
Geodon	Capsule	80 mg/1	Oral	Remedy Repack	2007-08-20	2012-07-19
Geodon	Capsule	80 mg/1	Oral	Physicians Total Care, Inc.	2006-05-25	2011-06-30
Geodon	Capsule	60 mg/1	Oral	Roerig	2019-08-01	Not applicable
Geodon	Capsule	80 mg/1	Oral	Rebel Distributors	2001-02-05	Not applicable

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products

Name	Dosage	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Auro-ziprasidone	Capsule	Oral	Auro Pharma Inc	2018-03-19	Not applicable
Auro-ziprasidone	Capsule	Oral	Auro Pharma Inc	2018-03-19	Not applicable
Auro-ziprasidone	Capsule	Oral	Auro Pharma Inc	2018-03-19	Not applicable
Auro-ziprasidone	Capsule	Oral	Auro Pharma Inc	2018-03-19	Not applicable
Gd-ziprasidone	Capsule	Oral	Genmed A Division Of Pfizer Canada Ulc	Not applicable	Not applicable
Gd-ziprasidone	Capsule	Oral	Genmed A Division Of Pfizer Canada Ulc	Not applicable	Not applicable
Gd-ziprasidone	Capsule	Oral	Genmed A Division Of Pfizer Canada Ulc	Not applicable	Not applicable
Gd-ziprasidone	Capsule	Oral	Genmed A Division Of Pfizer Canada Ulc	Not applicable	Not applicable
Mylan-ziprasidone	Capsule	Oral	Mylan Pharmaceuticals	Not applicable	Not applicable
Mylan-ziprasidone	Capsule	Oral	Mylan Pharmaceuticals	Not applicable	Not applicable

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

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Categories

UNII

6UKA5VEJ6X

CAS number

146939-27-7

Weight

Average: 412.936
Monoisotopic: 412.112459711

Chemical Formula

C₂₁H₂₁ClN₄OS

InChI Key

MVWVFYHBGMAFLY-UHFFFAOYSA-N

InChI

InChI=1S/C21H21ClN4OS/c22-17-13-18-15(12-20(27)23-18)11-14(17)5-6-25-7-9-26(10-8-25)21-16-3-1-2-4-19(16)28-24-21/h1-4,11,13H,5-10,12H2,(H,23,27)

IUPAC Name

5-{2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl}-6-chloro-2,3-dihydro-1H-indol-2-one

SMILES

ClC1=C(CCN2CCN(CC2)C2=NSC3=CC=CC=C23)C=C2CC(=O)NC2=C1

Pharmacology

Indication

In its oral form, ziprasidone is approved for the treatment of schizophrenia, as monotherapy for acute treatment of manic or mixed episodes related to bipolar I disorder, and as adjunctive therapy to lithium or valproate for maintenance treatment of bipolar I disorder.¹³ The injectable formulation is approved only for treatment of acute agitation in schizophrenia.¹³

Associated Conditions

Pharmacodynamics

Ziprasidone is classified as a "second generation" or "atypical" antipsychotic and is a dopamine and 5HT2A receptor antagonist with a unique receptor binding profile. As previously mentioned, ziprasidone has a very high 5-HT2A/D2 affinity ratio, binds to multiple serotonin receptors in addition to 5-HT2A, and blocks monoamine transporters which prevents 5HT and NE reuptake. On the other hand, ziprasidone has a low affinity for muscarinic cholinergic M1, histamine H1, and alpha1-adrenergic receptors.⁴

Mechanism of action

The effects of ziprasidone are differentiated from other antispychotics based on its preference and affinity for certain receptors. Ziprasidone binds to serotonin-2A (5-HT2A) and dopamine D2 receptors in a similar fashion to other atypical antipsychotics; however, one key difference is that ziprasidone has a higher 5-HT2A/D2 receptor affinity ratio when compared to other antipsychotics such as olanzapine, quetiapine, risperidone, and aripiprazole.¹ Ziprasidone offers enhanced modulation of mood, notable negative symptom relief, overall cognitive improvement and reduced motor dysfunction which is linked to it's potent interaction with 5-HT2C, 5-HT1D, and 5-HT1A receptors in brain tissue.¹ Ziprasidone can bind moderately to norepinephrine and serotonin reuptake sites which may contribute to its antidepressant and anxiolytic activity.¹ Patient's taking ziprasidone will likely experience a lower incidence of orthostatic hypotension, cognitive disturbance, sedation, weight gain, and disruption in prolactin levels since ziprasidone has a lower affinity for histamine H1, muscarinic M1, and alpha1-adrenoceptors.¹

Target	Actions	Organism
ADopamine D2 receptor	antagonist	Humans
UDopamine D1 receptor	antagonist	Humans
UDopamine D5 receptor	antagonist	Humans
A5-hydroxytryptamine receptor 2A	antagonist	Humans
UDopamine D3 receptor	antagonist	Humans
UDopamine D4 receptor	antagonist	Humans
A5-hydroxytryptamine receptor 1A	agonist	Humans
U5-hydroxytryptamine receptor 1B	antagonist	Humans
U5-hydroxytryptamine receptor 1D	antagonist	Humans
U5-hydroxytryptamine receptor 1E	antagonist	Humans
U5-hydroxytryptamine receptor 2C	antagonist	Humans
U5-hydroxytryptamine receptor 3A	antagonist	Humans
U5-hydroxytryptamine receptor 6	antagonist	Humans
U5-hydroxytryptamine receptor 7	antagonist	Humans
NHistamine H1 receptor	antagonist	Humans
NAlpha-1A adrenergic receptor	antagonist	Humans
NAlpha-1B adrenergic receptor	antagonist	Humans
NAlpha-2A adrenergic receptor	antagonist	Humans
NAlpha-2B adrenergic receptor	antagonist	Humans
NAlpha-2C adrenergic receptor	antagonist	Humans
NMuscarinic acetylcholine receptor M1	antagonist	Humans
NMuscarinic acetylcholine receptor M2	antagonist	Humans
NMuscarinic acetylcholine receptor M3	antagonist	Humans
NMuscarinic acetylcholine receptor M4	antagonist	Humans
NMuscarinic acetylcholine receptor M5	antagonist	Humans

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Additional Data Available

Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

In the absence of food, ziprasidone's oral bioavailability is 60%, and absorption may reach 100% if ziprasidone is taken with a meal containing at least 500 kcal. The difference in bioavailability has little to do with the fat content of the food and appears to be related to the bulk of the meal since more absorption occurs the longer ziprasidone remains in the stomach.⁴

Volume of distribution

The mean apparent volume of distribution of Ziprasidone is 1.5 L/kg.¹³

Protein binding

Ziprasidone is extensively protein bound with over 99% of the drug bound to plasma proteins, primarily albumin and alpha1-acid glycoprotein.^11,13

Metabolism

Ziprasidone is heavily metabolized in the liver with less than 5% of the drug excreted unchanged in the urine.³ The primary reductive pathway is catalyzed by aldehyde oxidase, while 2 other less prominent oxidative pathways are catalyzed by CYP3A4.³ Ziprasidone is unlikely to interact with other medications metabolized by CYP3A4 since only 1/3 of the antipsychotic is metabolized by the CYP3A4 system.³

There are 12 identified ziprasidone metabolites (abbreviations italicized): Ziprasidone sulfoxide, ziprasidone sulfone, (6-chloro-2-oxo-2,3-dihydro-1H-indol-5-yl)acetic acid (OX-COOH), OX-COOH glucuronide, 3-(piperazine-1-yl)-1,2-benzisothiazole (BITP), BITP sulfoxide, BITP sulfone, BITP sulfone lactam, S-Methyl-dihydro-ziprasidone, S-Methyl-dihydro-ziprasidone-sulfoxide, 6-chloro-5-(2-piperazin-1-yl-ethyl)-1,3-dihydro-indol-2-one (OX-P), and dihydro-ziprasidone-sulfone.¹⁰

As suggested by the quantity of metabolites, ziprasidone is metabolized through several different pathways. Ziprasidone is sequentially oxidized to ziprasidone sulfoxide and ziprasidone sulfone, and oxidative N-dealkylation of ziprasidone produces OX-COOH and BITP.¹⁰ OX-COOH undergoes phase II metabolism to yield a glucuronidated metabolite while BITP is sequentially oxidized into BITP sulfoxide, BITP sulfone, then BITP sulfone lactam.¹⁰ Ziprasidone can also undergo reductive cleavage and methylation to produce S-Methyl-dihydro-ziprasidone and then further oxidation to produce S-Methyl-dihydro-ziprasidone-sulfoxide.¹⁰ Finally dearylation of ziprasidone produces OX-P, and the process of hydration and oxidation transforms the parent drug into dihydro-ziprasidone-sulfone.¹⁰

Although CYP3A4 and aldehyde oxidase are the primary enzymes involved in ziprasidone metabolism³, the pathways associated with each enzyme have not been specified.

Route of elimination

Ziprasidone is extensively metabolized after oral administration with only a small amount excreted in the urine (<1%) or feces (<4%) as unchanged drug.

Half life

The half life of ziprasidone is 6-7 hours.⁴

Clearance

The mean apparent systemic clearance is 7.5 mL/min/kg.¹³

Toxicity

The most common adverse reactions reported with ziprasidone include somnolence, respiratory tract infections, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, vomiting, headache and nausea. ¹³

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
Unlock Additional Data
(R)-warfarin	The serum concentration of (R)-warfarin can be increased when it is combined with Ziprasidone.
(S)-Warfarin	The serum concentration of (S)-Warfarin can be increased when it is combined with Ziprasidone.
1-benzylimidazole	The risk or severity of hypertension can be increased when Ziprasidone is combined with 1-benzylimidazole.
1,10-Phenanthroline	The therapeutic efficacy of Ziprasidone can be decreased when used in combination with 1,10-Phenanthroline.
2,4-thiazolidinedione	The therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Ziprasidone.
2,5-Dimethoxy-4-ethylamphetamine	The therapeutic efficacy of Ziprasidone can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine	The risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Ziprasidone.
3,5-Dinitrocatechol	The therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Ziprasidone.
4-Bromo-2,5-dimethoxyamphetamine	The risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Ziprasidone.
4-Bromo-2,5-dimethoxyphenethylamine	The therapeutic efficacy of 4-Bromo-2,5-dimethoxyphenethylamine can be decreased when used in combination with Ziprasidone.

Additional Data Available

Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

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Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

Avoid alcohol.

References

Synthesis Reference

Frank R. Busch, Carol A. Rose, "Mesylate trihydrate salt of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)ethyl)-6-chloro-1,3-dihy dro-2(1H)-indol-2-one (=ziprasidone), its preparation and its use as dopamine D2 antagonist." U.S. Patent US6110918, issued January, 1995.

US6110918

General References

Stahl SM, Shayegan DK: The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice. J Clin Psychiatry. 2003;64 Suppl 19:6-12. [PubMed:14728084]
Schmidt AW, Lebel LA, Howard HR Jr, Zorn SH: Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile. Eur J Pharmacol. 2001 Aug 17;425(3):197-201. [PubMed:11513838]
Beedham C, Miceli JJ, Obach RS: Ziprasidone metabolism, aldehyde oxidase, and clinical implications. J Clin Psychopharmacol. 2003 Jun;23(3):229-32. doi: 10.1097/01.jcp.0000084028.22282.f2. [PubMed:12826984]
Mattei C, Rapagnani MP, Stahl SM: Ziprasidone hydrocloride: what role in the management of schizophrenia? J Cent Nerv Syst Dis. 2011 Feb 15;3:1-16. doi: 10.4137/JCNSD.S4138. Print 2011. [PubMed:23861634]
Bouchette D, Marwaha R: Ziprasidone . [PubMed:28846230]
Kutcher S, Brooks SJ, Gardner DM, Honer B, Kopala L, Labelle A, Lalonde P, Malla A, Milliken H, Soni J, Williams R: Expert Canadian consensus suggestions on the rational, clinical use of ziprasidone in the treatment of schizophrenia and related psychotic disorders. Neuropsychiatr Dis Treat. 2005 Jun;1(2):89-108. doi: 10.2147/nedt.1.2.89.61042. [PubMed:18568067]
Murray R, Correll CU, Reynolds GP, Taylor D: Atypical antipsychotics: recent research findings and applications to clinical practice: Proceedings of a symposium presented at the 29th Annual European College of Neuropsychopharmacology Congress, 19 September 2016, Vienna, Austria. Ther Adv Psychopharmacol. 2017 Mar;7(1 Suppl):1-14. doi: 10.1177/2045125317693200. Epub 2017 Mar 1. [PubMed:28344764]
Dayabandara M, Hanwella R, Ratnatunga S, Seneviratne S, Suraweera C, de Silva VA: Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Neuropsychiatr Dis Treat. 2017 Aug 22;13:2231-2241. doi: 10.2147/NDT.S113099. eCollection 2017. [PubMed:28883731]
Wilner KD, Demattos SB, Anziano RJ, Apseloff G, Gerber N: Ziprasidone and the activity of cytochrome P450 2D6 in healthy extensive metabolizers. Br J Clin Pharmacol. 2000;49 Suppl 1:43S-47S. [PubMed:10771453]
Prakash C, Kamel A, Gummerus J, Wilner K: Metabolism and excretion of a new antipsychotic drug, ziprasidone, in humans. Drug Metab Dispos. 1997 Jul;25(7):863-72. [PubMed:9224781]
Uzelac TN, Nikolic-Kokic AL, Spasic SD, Macvanin MT, Nikolic MR, Mandic LM, Jovanovic VB: Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content. Chem Biol Interact. 2019 Sep 25;311:108787. doi: 10.1016/j.cbi.2019.108787. Epub 2019 Aug 7. [PubMed:31400341]
Ziprasidone Black Box Warning [Link]
FDA Approved Drug Products: Geodon (ziprasidone HCl) [Link]
Zeldox Pfizer Canada Product Monograph [Link]
FDA Approved Drug Products: Geodon (ziprasidone) [Link]

External Links

Human Metabolome Database: HMDB0014391
KEGG Drug: D08687
KEGG Compound: C07568
PubChem Compound: 60854
PubChem Substance: 46507627
ChemSpider: 54841
BindingDB: 50048803
RxNav: 115698
ChEBI: 10119
ChEMBL: CHEMBL708
ZINC: ZINC000000538550
Therapeutic Targets Database: DAP000079
PharmGKB: PA451974
Guide to Pharmacology: GtP Drug Page
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Ziprasidone

ATC Codes

N05AE04 — Ziprasidone

AHFS Codes

28:16.08.04 — Atypical Antipsychotics

MSDS

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Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Recruiting	Prevention	Opioid Abuse, Unspecified / Opioid Dependence	1
1	Completed	Basic Science	Healthy Volunteers	1
1	Completed	Treatment	Healthy Volunteers	2
1	Recruiting	Diagnostic	Schizophrenia	1
1	Terminated	Prevention	Cardiovascular Heart Disease	1
1, 2	Recruiting	Basic Science	Schizophrenia	1
2	Completed	Treatment	Autism, Early Infantile	1
2	Completed	Treatment	Bipolar Disorder (BD) / Depression / Depression, Bipolar	1
2	Completed	Treatment	Bipolar Disorder (BD) / Schizoaffective Disorders / Schizophrenia	1
2	Completed	Treatment	Borderline Personality Disorder (BPD)	1
2	Completed	Treatment	Cognition Disorders / Delirium	1
2	Completed	Treatment	Major Depressive Disorder (MDD)	2
2	Completed	Treatment	Oppositional Defiant Disorder	1
2	Completed	Treatment	Psychosis Prodrome	1
2	Completed	Treatment	Schizophrenia	3
2	Completed	Treatment	Social Anxiety Disorder (SAD)	1
2	Terminated	Not Available	Post Traumatic Stress Disorder (PTSD)	1
2	Terminated	Treatment	Schizophrenia	1
2, 3	Completed	Treatment	Affective Disorders	1
2, 3	Completed	Treatment	Schizoaffective Disorders / Schizophrenia	1
3	Completed	Treatment	Bipolar Disorder (BD)	5
3	Completed	Treatment	Bipolar affective disorder, manic / Bipolar Disorder (BD)	1
3	Completed	Treatment	Bipolar Disorder (BD) / Depression, Bipolar	1
3	Completed	Treatment	Bipolar Disorder (BD) / Major Depressive Disorder (MDD) / Psychosis / Schizoaffective Disorders / Schizophreniform Disorder	1
3	Completed	Treatment	Bipolar I Disorder	1
3	Completed	Treatment	Delirium / Impaired Cognition / Long Term Psychologic Disorders	1
3	Completed	Treatment	Depression	1
3	Completed	Treatment	Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenia	1
3	Completed	Treatment	Psychotic Disorder NOS / Schizophrenia	1
3	Completed	Treatment	Schizophrenia	8
3	Completed	Treatment	Schizophrenia and Schizoaffective Disorder	1
3	Recruiting	Treatment	Bipolar Disorder (BD)	2
3	Terminated	Treatment	Anxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenia	1
3	Terminated	Treatment	Bipolar Disorder (BD)	1
3	Terminated	Treatment	Bipolar Disorder (BD) / Schizoaffective Disorders / Schizophrenia	1
3	Terminated	Treatment	Schizoaffective Disorders / Schizophrenia	1
3	Terminated	Treatment	Schizophrenia	3
3	Unknown Status	Treatment	Psychosis Nos/Other	1
3	Withdrawn	Treatment	Bipolar Disorder (BD)	2
4	Completed	Not Available	Healthy Male Volunteers	1
4	Completed	Basic Science	Diabetes / Schizophrenia	1
4	Completed	Diagnostic	Post Traumatic Stress Disorder (PTSD) / Posttraumatic Stress Disorders	1
4	Completed	Treatment	Acute Exacerbation of Psychosis / Delusional Disorder / Mania / Schizophrenia	1
4	Completed	Treatment	Affective Disorders / Psychotic Disorder NOS / Psychotic Mood Disorder / Schizophrenia	1
4	Completed	Treatment	Bipolar Disorder (BD)	3
4	Completed	Treatment	Bipolar Disorder (BD) / Depression	1
4	Completed	Treatment	Bipolar Disorder (BD) / Generalized Anxiety Disorder (GAD) / Panic Disorders	1
4	Completed	Treatment	Bipolar Disorder (BD) / Mania	1
4	Completed	Treatment	Bipolar Disorder (BD) / Medication Adherence	1
4	Completed	Treatment	Bipolar II Disorder / Major Depressive Episode	1
4	Completed	Treatment	Depression, Bipolar	1
4	Completed	Treatment	Depression / Schizoaffective Disorders / Schizophrenia	1
4	Completed	Treatment	First Episode Psychosis	1
4	Completed	Treatment	Insulin Resistance / Metabolic Syndromes / Schizophrenia	1
4	Completed	Treatment	Psychotic Disorder NOS	2
4	Completed	Treatment	Psychotic Disorder NOS / Schizophrenia	4
4	Completed	Treatment	Pyschotic Disorders	1
4	Completed	Treatment	Schizoaffective Disorders / Schizophrenia	6
4	Completed	Treatment	Schizoaffective Disorders / Schizophrenia / Schizophrenia and Disorders With Psychotic Features	1
4	Completed	Treatment	Schizophrenia	8
4	Completed	Treatment	Schizophrenia, Schizoaffective Disorder	1
4	Not Yet Recruiting	Treatment	Schizophrenia	1
4	Recruiting	Treatment	Bipolar Disorder (BD)	1
4	Recruiting	Treatment	Schizophrenia	1
4	Terminated	Not Available	High Risk MC4R Genotype / Low Risk MC4R Genotype / One Week or Less Antipsychotic Lifetime Exposure	1
4	Terminated	Treatment	Acute Mania / Bipolar Disorder, Manic	1
4	Terminated	Treatment	Bipolar Disorder (BD) / Generalized Anxiety Disorder (GAD)	1
4	Terminated	Treatment	Schizophrenia and Disorders With Psychotic Features	1
4	Unknown Status	Treatment	Schizophrenia	1
4	Unknown Status	Treatment	Schizophrenia or Schizoaffective Disorder	1
4	Withdrawn	Treatment	Agitation / Delirium / Psychosis	1
Not Available	Completed	Not Available	Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB) / Acute Bacterial Sinusitis (ABS) / Acute Decompensated Heart Failure (ADHF) / Acute Pyelonephritis / Adenovirus / Adjunct to general anesthesia therapy / Adrenal Insufficiency / Airway Swelling / Anaesthesia therapy / Anxiety / Anxiolysis / Autism, Early Infantile / Autistic Disorder / Bartonellosis / Benzodiazepine Withdrawal / Benzodiazepines / Bipolar Disorder (BD) / Bloodstream Infections / Bone and Joint Infections / Bradycardia / Brain Swelling / Bronchospasm / Brucellosis / Cardiac Arrest (CA) / Central Nervous System Infections / Cholera / Chronic Bacterial Prostatitis / Chronic Kidney Disease (CKD) / Community Acquired Pneumonia (CAP) / Complicated Urinary Tract Infection / Convulsions / Cytomegalovirus Retinitis / Drug hypersensitivity reaction / Dysrhythmia, Cardiac / Early-onset Schizophrenia Spectrum Disorders / Edema / Endocarditis / Epilepsies / Fibrinolytic Bleeding / Flu caused by Influenza / Gastroparesis / Gram-negative Infection / Gynaecological infection / Headache / Heart Failure / Heavy Menstrual Bleeding / Hemophilia / Herpes Simplex Virus / High Blood Pressure (Hypertension) / High Cholesterol / Hyperaldosteronism / Hyperlipidemias / Hypokalemia / Hypotension / Infantile Hemangiomas / Infection / Infection caused by staphylococci / Inflammatory Conditions / Inflammatory Reaction / Influenza Treatment or Prophylaxis / Inhalational Anthrax (Post-Exposure) / Insomnia / Intra-Abdominal Infections / Life-threatening Fungal Infections / Lower Respiratory Tract Infection (LRTI) / Meningitis, Bacterial / Methicillin Resistant Staphylococcus Aureus (MRSA) / Migraine / Muscle Spasms / Nausea / Neuromuscular Blockade / Neutropenia / Nosocomial Pneumonia / Opioid Addiction / Pain / Plague / Pneumonia / Prophylaxis / Psittacosis / Pulmonary Arterial Hypertension (PAH) / Q Fever / Reflux / Relapsing Fever / Rocky Mountain Spotted Fever / Schizophrenia / Sedation / Seizures / Sepsis / Skeletal Muscle Spasms / Skin and skin-structure infections / Skin and Subcutaneous Tissue Bacterial Infections / Stable Angina (SA) / Thromboprophylaxis / Thrombotic events / Toxic effect of hydrocyanic acid and cyanides / Trachoma / Treatment-resistant Schizophrenia / Tularemia / Typhus Fever / Uncomplicated Skin and Skin Structure Infections / Uncomplicated Urinary Tract Infections / Urinary Tract Infection / Vomiting / Withdrawal	1
Not Available	Completed	Not Available	Affective Psychosis, Bipolar / Mania / Psychoses, Manic-Depressive	1
Not Available	Completed	Not Available	Bipolar Disorder (BD)	1
Not Available	Completed	Not Available	Bipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenia / Type 2 Diabetes Mellitus	1
Not Available	Completed	Not Available	Bipolar Disorder (BD) / Schizophrenia	1
Not Available	Completed	Not Available	Psychomotor Agitation	2
Not Available	Completed	Not Available	Schizophrenia	2
Not Available	Completed	Diagnostic	Obsessive Compulsive Disorder (OCD) / Schizophrenia	1
Not Available	Completed	Prevention	Hyperglycemia / Hyperlipidemias	1
Not Available	Completed	Treatment	Bipolar Disorder (BD) / Schizoaffective Disorders / Schizophrenia	2
Not Available	Completed	Treatment	Hyperglycemia / Schizoaffective Disorders / Schizophrenia / Type 2 Diabetes Mellitus	1
Not Available	Completed	Treatment	Psychomotor Agitation	1
Not Available	Completed	Treatment	Schizophrenia	3
Not Available	Completed	Treatment	Schizophrenia / Type 2 Diabetes Mellitus	1
Not Available	Enrolling by Invitation	Not Available	Bipolar Disorder (BD)	1
Not Available	Recruiting	Not Available	Adverse Drug Effect of Antipsychotics and Neuroleptics / Efficacy / Individualed Opitmal Therapy / Schizophrenia	1
Not Available	Recruiting	Not Available	Micrognathia / Schizophrenia	1

Pharmacoeconomics

Manufacturers

Pfizer inc

Packagers

Ben Venue Laboratories Inc.
Cardinal Health
Comprehensive Consultant Services Inc.
Kaiser Foundation Hospital
Lake Erie Medical and Surgical Supply
Nucare Pharmaceuticals Inc.
Pfizer Inc.
Pharmacia Inc.
Physicians Total Care Inc.
Prepackage Specialists
Rebel Distributors Corp.
Remedy Repack
Resource Optimization and Innovation LLC
Stat Rx Usa
US Pharmaceutical Group

Dosage forms

Form	Route	Strength
Capsule	Oral	20 mg/1
Capsule	Oral	40 mg/1
Capsule	Oral	60 mg/1
Capsule	Oral	80 mg/1
Injection, powder, lyophilized, for solution	Intramuscular	20 mg/1mL
Capsule	Oral

Prices

Unit description	Cost	Unit
Zoladex 10.8 mg Implant Syringe	1407.72USD	syringe
Geodon 20 mg vial	16.22USD	vial
Geodon 60 mg capsule	9.88USD	capsule
Geodon 80 mg capsule	9.88USD	capsule
Geodon 20 mg capsule	8.14USD	capsule
Geodon 40 mg capsule	8.14USD	capsule
Zeldox 40 mg Capsule	2.13USD	capsule
Zeldox 60 mg Capsule	2.13USD	capsule
Zeldox 80 mg Capsule	2.13USD	capsule
Zeldox 20 mg Capsule	1.86USD	capsule

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Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
Unlock Additional Data
US5134127	No	1992-07-28	2010-01-23
CA2256227	No	2003-07-01	2018-12-16
CA2105114	No	2000-02-15	2013-08-30
US6245766	No	2001-06-12	2018-12-18
US6150366	No	2000-11-21	2019-05-27
US6232304	No	2001-05-15	2017-04-01
US6399777	No	2002-06-04	2017-04-01
US6110918	No	2000-08-29	2017-03-26
US7175855	No	2007-02-13	2020-05-18

Additional Data Available

Filed On

The date on which a patent was filed with the relevant government.

Learn more

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	>276°C (Ziprasidone Hydrochloride Monohydrate)	https://www.trc-canada.com/product-detail/?CatNum=Z485000
logP	3.8	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.00718 mg/mL	ALOGPS
logP	4.64	ALOGPS
logP	4.3	ChemAxon
logS	-4.8	ALOGPS
pKa (Strongest Acidic)	13.18	ChemAxon
pKa (Strongest Basic)	7.09	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	48.47 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	116.72 m³·mol^-1	ChemAxon
Polarizability	44.96 Å³	ChemAxon
Number of Rings	5	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	1.0
Blood Brain Barrier	+	0.9759
Caco-2 permeable	+	0.8867
P-glycoprotein substrate	Substrate	0.7167
P-glycoprotein inhibitor I	Inhibitor	0.8052
P-glycoprotein inhibitor II	Inhibitor	0.6419
Renal organic cation transporter	Inhibitor	0.5325
CYP450 2C9 substrate	Non-substrate	0.7972
CYP450 2D6 substrate	Non-substrate	0.9117
CYP450 3A4 substrate	Substrate	0.7408
CYP450 1A2 substrate	Inhibitor	0.6576
CYP450 2C9 inhibitor	Inhibitor	0.6329
CYP450 2D6 inhibitor	Non-inhibitor	0.7151
CYP450 2C19 inhibitor	Inhibitor	0.8086
CYP450 3A4 inhibitor	Non-inhibitor	0.7723
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.9567
Ames test	Non AMES toxic	0.6273
Carcinogenicity	Non-carcinogens	0.8672
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.5877 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.6826
hERG inhibition (predictor II)	Inhibitor	0.7753

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-01ox-0900400000-0a17dd0e237f50ba91c5

Taxonomy

Description: This compound belongs to the class of organic compounds known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.
Kingdom: Organic compounds
Super Class: Organoheterocyclic compounds
Class: Diazinanes
Sub Class: Piperazines
Direct Parent: N-arylpiperazines
Alternative Parents: Benzothiazoles / Phenethylamines / Indoles / Dialkylarylamines / Aralkylamines / N-alkylpiperazines / Aminothiazoles / Aryl chlorides / Imidolactams / Heteroaromatic compounds
show 8 more
Substituents: N-arylpiperazine / 1,2-benzothiazole / Indole / Indole or derivatives / Phenethylamine / Dialkylarylamine / N-alkylpiperazine / Aralkylamine / Imidolactam / Benzenoid
show 22 more
Molecular Framework: Aromatic heteropolycyclic compounds
External Descriptors: organochlorine compound, indolones, piperazines, 1,2-benzisothiazole (CHEBI:10119)

Targets

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	5	N/A	N/A	16220969
Ki (nM)	2.8	N/A	N/A	11170639
Ki (nM)	3.1	N/A	N/A	18595716
Ki (nM)	5	N/A	N/A	18160289
Ki (nM)	8.5	N/A	N/A	23043306
Ki (nM)	9.7	N/A	N/A	14998318

Details1. Dopamine D2 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Potassium channel regulator activity
Specific Function: Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name: DRD2
Uniprot ID: P14416
Uniprot Name: D(2) dopamine receptor
Molecular Weight: 50618.91 Da

References

Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed:11873706]
Kopecek M, Bares M, Mohr P: Ziprasidone-induced galactorrhea: a case report. Neuro Endocrinol Lett. 2005 Feb;26(1):69-70. [PubMed:15726024]
Seeger TF, Seymour PA, Schmidt AW, Zorn SH, Schulz DW, Lebel LA, McLean S, Guanowsky V, Howard HR, Lowe JA 3rd, et al.: Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. J Pharmacol Exp Ther. 1995 Oct;275(1):101-13. [PubMed:7562537]
Stahl SM, Shayegan DK: The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice. J Clin Psychiatry. 2003;64 Suppl 19:6-12. [PubMed:14728084]
Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	130	N/A	N/A	18595716
Ki (nM)	330	N/A	N/A	14998318
Ki (nM)	9.5	N/A	N/A	11170639

Details2. Dopamine D1 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: G-protein coupled amine receptor activity
Specific Function: Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name: DRD1
Uniprot ID: P21728
Uniprot Name: D(1A) dopamine receptor
Molecular Weight: 49292.765 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Details3. Dopamine D5 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: G-protein coupled amine receptor activity
Specific Function: Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name: DRD5
Uniprot ID: P21918
Uniprot Name: D(1B) dopamine receptor
Molecular Weight: 52950.5 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	0.42	N/A	N/A	16220969
Ki (nM)	0.08	N/A	N/A	18160289
Ki (nM)	0.12	N/A	N/A	11132243
Ki (nM)	0.25	N/A	N/A	11170639
Ki (nM)	0.3	N/A	N/A	12629531 / 14998318
Ki (nM)	0.39	N/A	N/A	18595716
Ki (nM)	0.5	N/A	N/A	12176106
Ki (nM)	1.4	N/A	N/A	8935801

Details4. 5-hydroxytryptamine receptor 2A

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Virus receptor activity
Specific Function: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name: HTR2A
Uniprot ID: P28223
Uniprot Name: 5-hydroxytryptamine receptor 2A
Molecular Weight: 52602.58 Da

References

Mansbach RS, Carver J, Zorn SH: Blockade of drug-induced deficits in prepulse inhibition of acoustic startle by ziprasidone. Pharmacol Biochem Behav. 2001 Jul-Aug;69(3-4):535-42. [PubMed:11509214]
Ichikawa J, Li Z, Dai J, Meltzer HY: Atypical antipsychotic drugs, quetiapine, iloperidone, and melperone, preferentially increase dopamine and acetylcholine release in rat medial prefrontal cortex: role of 5-HT1A receptor agonism. Brain Res. 2002 Nov 29;956(2):349-57. [PubMed:12445705]
Lu BY, Lundgren R, Escalona PR, Roberts BB: A case of ziprasidone-induced mania and the role of 5-HT2A in mood changes induced by atypical antipsychotics. J Clin Psychiatry. 2002 Dec;63(12):1185-6. [PubMed:12530423]
Mamo D, Kapur S, Shammi CM, Papatheodorou G, Mann S, Therrien F, Remington G: A PET study of dopamine D2 and serotonin 5-HT2 receptor occupancy in patients with schizophrenia treated with therapeutic doses of ziprasidone. Am J Psychiatry. 2004 May;161(5):818-25. [PubMed:15121646]
Kast RE, Focosi D, Petrini M, Altschuler EL: Treatment schedules for 5-HT2A blocking in progressive multifocal leukoencephalopathy using risperidone or ziprasidone. Bone Marrow Transplant. 2007 Jun;39(12):811-2. Epub 2007 Apr 23. [PubMed:17450180]
Stahl SM, Shayegan DK: The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice. J Clin Psychiatry. 2003;64 Suppl 19:6-12. [PubMed:14728084]
Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	10	N/A	N/A	11170639
Ki (nM)	7.2	N/A	N/A	18595716
Ki (nM)	7.5	N/A	N/A	14998318

Details5. Dopamine D3 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: G-protein coupled amine receptor activity
Specific Function: Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name: DRD3
Uniprot ID: P35462
Uniprot Name: D(3) dopamine receptor
Molecular Weight: 44224.335 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	32	N/A	N/A	18595716
Ki (nM)	39	N/A	N/A	11170639 / 14998318

Details6. Dopamine D4 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Sh3 domain binding
Specific Function: Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins ...
Gene Name: DRD4
Uniprot ID: P21917
Uniprot Name: D(4) dopamine receptor
Molecular Weight: 48359.86 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	1.9	N/A	N/A	11132243
Ki (nM)	12	N/A	N/A	8935801
Ki (nM)	2.5	N/A	N/A	18595716
Ki (nM)	37	N/A	N/A	11170639
Ki (nM)	4	N/A	N/A	18160289
Ki (nM)	76	N/A	N/A	12629531

Details7. 5-hydroxytryptamine receptor 1A

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: Serotonin receptor activity
Specific Function: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name: HTR1A
Uniprot ID: P08908
Uniprot Name: 5-hydroxytryptamine receptor 1A
Molecular Weight: 46106.335 Da

References

Sprouse JS, Reynolds LS, Braselton JP, Rollema H, Zorn SH: Comparison of the novel antipsychotic ziprasidone with clozapine and olanzapine: inhibition of dorsal raphe cell firing and the role of 5-HT1A receptor activation. Neuropsychopharmacology. 1999 Nov;21(5):622-31. [PubMed:10516958]
Rollema H, Lu Y, Schmidt AW, Sprouse JS, Zorn SH: 5-HT(1A) receptor activation contributes to ziprasidone-induced dopamine release in the rat prefrontal cortex. Biol Psychiatry. 2000 Aug 1;48(3):229-37. [PubMed:10924666]
Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
Wilner KD, Anziano RJ, Johnson AC, Miceli JJ, Fricke JR, Titus CK: The anxiolytic effect of the novel antipsychotic ziprasidone compared with diazepam in subjects anxious before dental surgery. J Clin Psychopharmacol. 2002 Apr;22(2):206-10. [PubMed:11910268]
Newman-Tancredi A, Rivet JM, Cussac D, Touzard M, Chaput C, Marini L, Millan MJ: Comparison of hippocampal G protein activation by 5-HT(1A) receptor agonists and the atypical antipsychotics clozapine and S16924. Naunyn Schmiedebergs Arch Pharmacol. 2003 Sep;368(3):188-99. Epub 2003 Aug 16. [PubMed:12923612]
Stahl SM, Shayegan DK: The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice. J Clin Psychiatry. 2003;64 Suppl 19:6-12. [PubMed:14728084]
Schmidt AW, Lebel LA, Howard HR Jr, Zorn SH: Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile. Eur J Pharmacol. 2001 Aug 17;425(3):197-201. [PubMed:11513838]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	0.99	N/A	N/A	8935801

Details8. 5-hydroxytryptamine receptor 1B

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Serotonin receptor activity
Specific Function: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name: HTR1B
Uniprot ID: P28222
Uniprot Name: 5-hydroxytryptamine receptor 1B
Molecular Weight: 43567.535 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]
Schmidt AW, Lebel LA, Howard HR Jr, Zorn SH: Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile. Eur J Pharmacol. 2001 Aug 17;425(3):197-201. [PubMed:11513838]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	2.4	N/A	N/A	11132243
Ki (nM)	5.1	N/A	N/A	8935801

Details9. 5-hydroxytryptamine receptor 1D

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Serotonin receptor activity
Specific Function: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name: HTR1D
Uniprot ID: P28221
Uniprot Name: 5-hydroxytryptamine receptor 1D
Molecular Weight: 41906.38 Da

References

Stahl SM, Shayegan DK: The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice. J Clin Psychiatry. 2003;64 Suppl 19:6-12. [PubMed:14728084]
Wilner KD, Anziano RJ, Johnson AC, Miceli JJ, Fricke JR, Titus CK: The anxiolytic effect of the novel antipsychotic ziprasidone compared with diazepam in subjects anxious before dental surgery. J Clin Psychopharmacol. 2002 Apr;22(2):206-10. [PubMed:11910268]
Seeger TF, Seymour PA, Schmidt AW, Zorn SH, Schulz DW, Lebel LA, McLean S, Guanowsky V, Howard HR, Lowe JA 3rd, et al.: Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. J Pharmacol Exp Ther. 1995 Oct;275(1):101-13. [PubMed:7562537]
Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
Sprouse JS, Reynolds LS, Braselton JP, Rollema H, Zorn SH: Comparison of the novel antipsychotic ziprasidone with clozapine and olanzapine: inhibition of dorsal raphe cell firing and the role of 5-HT1A receptor activation. Neuropsychopharmacology. 1999 Nov;21(5):622-31. [PubMed:10516958]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	360	N/A	N/A	8935801

Details10. 5-hydroxytryptamine receptor 1E

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Serotonin receptor activity
Specific Function: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that trig...
Gene Name: HTR1E
Uniprot ID: P28566
Uniprot Name: 5-hydroxytryptamine receptor 1E
Molecular Weight: 41681.57 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	0.55	N/A	N/A	11170639
Ki (nM)	0.72	N/A	N/A	18595716
Ki (nM)	0.9	N/A	N/A	11132243
Ki (nM)	13	N/A	N/A	12629531 / 14998318 / 20719507
Ki (nM)	4.1	N/A	N/A	10991983

Details11. 5-hydroxytryptamine receptor 2C

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Serotonin receptor activity
Specific Function: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name: HTR2C
Uniprot ID: P28335
Uniprot Name: 5-hydroxytryptamine receptor 2C
Molecular Weight: 51820.705 Da

References

Stahl SM, Shayegan DK: The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice. J Clin Psychiatry. 2003;64 Suppl 19:6-12. [PubMed:14728084]
Sanchez C, Arnt J: In-vivo assessment of 5-HT2A and 5-HT2C antagonistic properties of newer antipsychotics. Behav Pharmacol. 2000 Jun;11(3-4):291-8. [PubMed:11103883]
Seeger TF, Seymour PA, Schmidt AW, Zorn SH, Schulz DW, Lebel LA, McLean S, Guanowsky V, Howard HR, Lowe JA 3rd, et al.: Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. J Pharmacol Exp Ther. 1995 Oct;275(1):101-13. [PubMed:7562537]
Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
Wood MD, Scott C, Clarke K, Cato KJ, Patel N, Heath J, Worby A, Gordon L, Campbell L, Riley G, Davies CH, Gribble A, Jones DN: Pharmacological profile of antipsychotics at monoamine receptors: atypicality beyond 5-HT2A receptor blockade. CNS Neurol Disord Drug Targets. 2006 Aug;5(4):445-52. [PubMed:16918396]

Details12. 5-hydroxytryptamine receptor 3A

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Voltage-gated potassium channel activity
Specific Function: This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gate...
Gene Name: HTR3A
Uniprot ID: P46098
Uniprot Name: 5-hydroxytryptamine receptor 3A
Molecular Weight: 55279.835 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	60.9	N/A	N/A	12629531
Ki (nM)	61	N/A	N/A	20719507
Ki (nM)	76	N/A	N/A	18595716

Details13. 5-hydroxytryptamine receptor 6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Serotonin receptor activity
Specific Function: This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name: HTR6
Uniprot ID: P50406
Uniprot Name: 5-hydroxytryptamine receptor 6
Molecular Weight: 46953.625 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Details14. 5-hydroxytryptamine receptor 7

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Serotonin receptor activity
Specific Function: This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name: HTR7
Uniprot ID: P34969
Uniprot Name: 5-hydroxytryptamine receptor 7
Molecular Weight: 53554.43 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	15	N/A	N/A	8935801
Ki (nM)	4.6	N/A	N/A	11132243
Ki (nM)	43	N/A	N/A	12629531
Ki (nM)	47	N/A	N/A	18595716
Ki (nM)	5.3	N/A	N/A	14998318
Ki (nM)	510	N/A	N/A	11170639

Details15. Histamine H1 receptor

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Antagonist

General Function: Histamine receptor activity
Specific Function: In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name: HRH1
Uniprot ID: P35367
Uniprot Name: Histamine H1 receptor
Molecular Weight: 55783.61 Da

References

Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [PubMed:11132243]
Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Details16. Alpha-1A adrenergic receptor

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Antagonist

General Function: Protein heterodimerization activity
Specific Function: This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name: ADRA1A
Uniprot ID: P35348
Uniprot Name: Alpha-1A adrenergic receptor
Molecular Weight: 51486.005 Da

References

Andersohn F, Schmedt N, Weinmann S, Willich SN, Garbe E: Priapism associated with antipsychotics: role of alpha1 adrenoceptor affinity. J Clin Psychopharmacol. 2010 Feb;30(1):68-71. doi: 10.1097/JCP.0b013e3181c8273d. [PubMed:20075651]
Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Details17. Alpha-1B adrenergic receptor

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Antagonist

General Function: Protein heterodimerization activity
Specific Function: This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name: ADRA1B
Uniprot ID: P35368
Uniprot Name: Alpha-1B adrenergic receptor
Molecular Weight: 56835.375 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	154	N/A	N/A	11132243
Ki (nM)	160	N/A	N/A	8935801 / 12629531

Details18. Alpha-2A adrenergic receptor

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Antagonist

General Function: Thioesterase binding
Specific Function: Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name: ADRA2A
Uniprot ID: P08913
Uniprot Name: Alpha-2A adrenergic receptor
Molecular Weight: 48956.275 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	48	N/A	N/A	8935801 / 12629531

Details19. Alpha-2B adrenergic receptor

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Antagonist

General Function: Epinephrine binding
Specific Function: Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
Gene Name: ADRA2B
Uniprot ID: P18089
Uniprot Name: Alpha-2B adrenergic receptor
Molecular Weight: 49565.8 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	59	N/A	N/A	12629531
Ki (nM)	77	N/A	N/A	8935801

Details20. Alpha-2C adrenergic receptor

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Antagonist

General Function: Protein homodimerization activity
Specific Function: Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name: ADRA2C
Uniprot ID: P18825
Uniprot Name: Alpha-2C adrenergic receptor
Molecular Weight: 49521.585 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	>10000	N/A	N/A	11170639
Ki (nM)	300	N/A	N/A	14642972
Ki (nM)	5100	N/A	N/A	18595716

Details21. Muscarinic acetylcholine receptor M1

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Antagonist

General Function: Phosphatidylinositol phospholipase c activity
Specific Function: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name: CHRM1
Uniprot ID: P11229
Uniprot Name: Muscarinic acetylcholine receptor M1
Molecular Weight: 51420.375 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	2440	N/A	N/A	11132243
Ki (nM)	3000	N/A	N/A	14642972

Details22. Muscarinic acetylcholine receptor M2

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Antagonist

General Function: G-protein coupled acetylcholine receptor activity
Specific Function: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name: CHRM2
Uniprot ID: P08172
Uniprot Name: Muscarinic acetylcholine receptor M2
Molecular Weight: 51714.605 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	>10000	N/A	N/A	12629531
Ki (nM)	1300	N/A	N/A	14642972

Details23. Muscarinic acetylcholine receptor M3

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Antagonist

General Function: Receptor activity
Specific Function: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name: CHRM3
Uniprot ID: P20309
Uniprot Name: Muscarinic acetylcholine receptor M3
Molecular Weight: 66127.445 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	1600	N/A	N/A	14642972

Details24. Muscarinic acetylcholine receptor M4

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Antagonist

General Function: Guanyl-nucleotide exchange factor activity
Specific Function: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name: CHRM4
Uniprot ID: P08173
Uniprot Name: Muscarinic acetylcholine receptor M4
Molecular Weight: 53048.65 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Details25. Muscarinic acetylcholine receptor M5

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Antagonist

General Function: Phosphatidylinositol phospholipase c activity
Specific Function: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name: CHRM5
Uniprot ID: P08912
Uniprot Name: Muscarinic acetylcholine receptor M5
Molecular Weight: 60073.205 Da

References

Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [PubMed:17848919]

Enzymes

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Prakash C, Kamel A, Cui D, Whalen RD, Miceli JJ, Tweedie D: Identification of the major human liver cytochrome P450 isoform(s) responsible for the formation of the primary metabolites of ziprasidone and prediction of possible drug interactions. Br J Clin Pharmacol. 2000;49 Suppl 1:35S-42S. [PubMed:10771452]
Prior TI, Baker GB: Interactions between the cytochrome P450 system and the second-generation antipsychotics. J Psychiatry Neurosci. 2003 Mar;28(2):99-112. [PubMed:12670127]
Beedham C, Miceli JJ, Obach RS: Ziprasidone metabolism, aldehyde oxidase, and clinical implications. J Clin Psychopharmacol. 2003 Jun;23(3):229-32. doi: 10.1097/01.jcp.0000084028.22282.f2. [PubMed:12826984]

Details2. Aldehyde oxidase

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Substrate

General Function: Xanthine dehydrogenase activity
Specific Function: Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal...
Gene Name: AOX1
Uniprot ID: Q06278
Uniprot Name: Aldehyde oxidase
Molecular Weight: 147916.735 Da

References

Spina E, de Leon J: Metabolic drug interactions with newer antipsychotics: a comparative review. Basic Clin Pharmacol Toxicol. 2007 Jan;100(1):4-22. doi: 10.1111/j.1742-7843.2007.00017.x. [PubMed:17214606]

Carriers

Details1. Serum albumin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Toxic substance binding
Specific Function: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name: ALB
Uniprot ID: P02768
Uniprot Name: Serum albumin
Molecular Weight: 69365.94 Da

References

Uzelac TN, Nikolic-Kokic AL, Spasic SD, Macvanin MT, Nikolic MR, Mandic LM, Jovanovic VB: Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content. Chem Biol Interact. 2019 Sep 25;311:108787. doi: 10.1016/j.cbi.2019.108787. Epub 2019 Aug 7. [PubMed:31400341]

Details2. Alpha-1-acid glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Not Available
Specific Function: Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name: ORM1
Uniprot ID: P02763
Uniprot Name: Alpha-1-acid glycoprotein 1
Molecular Weight: 23511.38 Da

References

Lv D, Zhao M, Chen L, Yu D, Yun X, Yang Q, Huang X: An Inter-Ethnic Comparison Study of Ziprasidone Plasma Levels, Dosage and Clinical Response in Patients with Schizophrenia. Psychiatry Investig. 2017 May;14(3):360-367. doi: 10.4306/pi.2017.14.3.360. Epub 2017 May 16. [PubMed:28539955]
FDA Approved Drug Products: Geodon (ziprasidone HCl) [Link]

Transporters

Details1. P-glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Xenobiotic-transporting atpase activity
Specific Function: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

References

Lv D, Zhao M, Chen L, Yu D, Yun X, Yang Q, Huang X: An Inter-Ethnic Comparison Study of Ziprasidone Plasma Levels, Dosage and Clinical Response in Patients with Schizophrenia. Psychiatry Investig. 2017 May;14(3):360-367. doi: 10.4306/pi.2017.14.3.360. Epub 2017 May 16. [PubMed:28539955]

Drug created on June 13, 2005 07:24 / Updated on February 23, 2020 23:03

Ziprasidone

Identification

Structure for Ziprasidone (DB00246)

Pharmacology

Interactions

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Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

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Enzymes

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Carriers

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Transporters

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