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Identification
Name Ziprasidone
Accession Number DB00246 (APRD00540)
Type small molecule
Groups approved
Description

Ziprasidone (marketed as Geodon, Zeldox) was the fifth atypical antipsychotic to gain FDA approval (February 2001). Ziprasidone is Food and Drug Administration (FDA) approved for the treatment of schizophrenia, and the intramuscular injection form of ziprasidone is approved for acute agitation in schizophrenic patients. Ziprasidone has also received approval for acute treatment of mania associated with bipolar disorder. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Ziprasidone hydrochloride
  • Ziprasidone mesylate trihydrate
Brand names
  • Geodon
  • Geodon Oral
  • Zeldox
Brand name mixtures Not Available
Categories
  • Antipsychotics
  • Dopamine Antagonists
  • Serotonin Antagonists
  • Antipsychotic Agents
CAS number 146939-27-7
Weight Average: 412.936
Monoisotopic: 412.112459711
Chemical Formula C21H21ClN4OS
InChI Key InChIKey=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)
Plain Text
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=CC2=C(CC(=O)N2)C=C1CCN1CCN(CC1)C1=NSC2=C1C=CC=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Indoles and Indole Derivatives
  • Phenethylamines
  • Lactams
Substructures
  • Indoles and Indole Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Piperazines
  • Benzene and Derivatives
  • Aryl Halides
  • Carboxylic Acids and Derivatives
  • Halobenzenes
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Lactams
  • Anilines
  • Pyrrolines
Pharmacology
Indication For the treatment of schizophrenia and related psychotic disorders.
Pharmacodynamics Ziprasidone is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Ziprasidone is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Ziprasidone acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other therapeutic and side effects of Ziprasidone. Ziprasidone's antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Ziprasidone's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Ziprasidone's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug. Ziprasidone functions as an antagonist at the Dopamine D2 , 5HT-2A , and 5HT-1D receptors, and as an agonist at the 5HT-1A receptor. Ziprasidone also inhibits synaptic reuptake of serotonin and norepinephrine.
Mechanism of action Ziprasidone's antipsychotic activity is likely due to a combination of its antagonistic function at D2 receptors in the mesolimbic pathways and at 5HT2A receptors in the frontal cortex. Alleviation of positive symptoms is due to antagonism at D2 receptors while relief of negative symptoms are due to 5HT2A antagonism.
Absorption ~60%
Volume of distribution
  • 1.5 L/kg
Protein binding 99%
Metabolism

Hepatic

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 3A4 benzisothiazole piperazine oxidation 843.5 3.7
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. Approximately 20% of the dose is excreted in the urine, with approximately 66% being eliminated in the feces.
Half life 7 hours
Clearance
  • 7.5 mL/min/kg
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Pfizer inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Powder, for solution Intramuscular
Prices
Unit description Cost Unit
Zoladex 10.8 mg Implant Syringe 1407.72 USD syringe
Geodon 20 mg vial 16.22 USD vial
Geodon 60 mg capsule 9.88 USD capsule
Geodon 80 mg capsule 9.88 USD capsule
Geodon 20 mg capsule 8.14 USD capsule
Geodon 40 mg capsule 8.14 USD capsule
Zeldox 40 mg Capsule 2.13 USD capsule
Zeldox 60 mg Capsule 2.13 USD capsule
Zeldox 80 mg Capsule 2.13 USD capsule
Zeldox 20 mg Capsule 1.86 USD capsule
Patents
Country Patent Number Approved Expires
United States 7175855 2000-05-18 2020-05-18
United States 5134127 1993-01-23 2010-01-23
Canada 2256227 2003-07-01 2018-12-16
Canada 2105114 2000-02-15 2013-08-30
Properties
State solid
Melting point >300 oC
Experimental Properties
Property Value Source
logP 3.8 PhysProp
Predicted Properties
Property Value Source
water solubility 7.18e-03 g/l ALOGPS
logP 4.64 ALOGPS
logP 4.30 ChemAxon Molconvert
logS -4.76 ALOGPS
pKa 14.89 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 48.47 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 116.72 ChemAxon Molconvert
polarizability 44.96 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. 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
External Links
Resource Link
KEGG Compound C07568 Link_out
PubChem Compound 60854 Link_out
PubChem Substance 46507627 Link_out
ChemSpider 54841 Link_out
ChEBI 10119 Link_out
ChEMBL 10119 Link_out
Therapeutic Targets Database DAP000079 Link_out
PharmGKB PA451974 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic2/ziprasidone.htm Link_out
Drugs.com http://www.drugs.com/cdi/ziprasidone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Ziprasidone Link_out
ATC Codes
  • N05AE04
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (75 KB)
MSDS show (57.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
Targets

1. D(2) dopamine receptor

Pharmacological action: yes
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out
Gene: DRD2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. Pubmed
  2. Kopecek M, Bares M, Mohr P: Ziprasidone-induced galactorrhea: a case report. Neuro Endocrinol Lett. 2005 Feb;26(1):69-70. Pubmed
  3. 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
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  5. 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
  6. 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

2. 5-hydroxytryptamine 2A receptor

Pharmacological action: yes
Actions: antagonist

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 mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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

3. D(1A) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P21728 Link_out
Gene: DRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

4. D(1B) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P21918 Link_out
Gene: DRD5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

5. D(3) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P35462 Link_out
Gene: DRD3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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

6. D(4) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P21917 Link_out
Gene: DRD4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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

7. 5-hydroxytryptamine 1A receptor

Pharmacological action: unknown
Actions: antagonist

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 is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P08908 Link_out
Gene: HTR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. Rollema H, Lu Y, Schmidt AW, Sprouse JS, Zorn SH: 5-HT receptor activation contributes to ziprasidone-induced dopamine release in the rat prefrontal cortex. Biol Psychiatry. 2000 Aug 1;48(3):229-37. Pubmed
  3. 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
  4. 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
  5. Newman-Tancredi A, Rivet JM, Cussac D, Touzard M, Chaput C, Marini L, Millan MJ: Comparison of hippocampal G protein activation by 5-HT receptor agonists and the atypical antipsychotics clozapine and S16924. Naunyn Schmiedebergs Arch Pharmacol. 2003 Sep;368(3):188-99. Epub 2003 Aug 16. Pubmed
  6. 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

8. 5-hydroxytryptamine 1B receptor

Pharmacological action: unknown
Actions: antagonist

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 is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P28222 Link_out
Gene: HTR1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

9. 5-hydroxytryptamine 1D receptor

Pharmacological action: unknown
Actions: antagonist

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 is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P28221 Link_out
Gene: HTR1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

10. 5-hydroxytryptamine 1E receptor

Pharmacological action: unknown
Actions: antagonist

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 is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P28566 Link_out
Gene: HTR1E Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

11. 5-hydroxytryptamine 2C receptor

Pharmacological action: unknown
Actions: antagonist

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 mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P28335 Link_out
Gene: HTR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

12. 5-hydroxytryptamine 3 receptor

Pharmacological action: unknown
Actions: antagonist

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-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel

Organism class: human
UniProt ID: P46098 Link_out
Gene: HTR3A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

13. 5-hydroxytryptamine 6 receptor

Pharmacological action: unknown
Actions: antagonist

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 is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs

Organism class: human
UniProt ID: P50406 Link_out
Gene: HTR6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

14. 5-hydroxytryptamine 7 receptor

Pharmacological action: unknown
Actions: antagonist

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 is mediated by G proteins that stimulate adenylate cyclase

Organism class: human
UniProt ID: P34969 Link_out
Gene: HTR7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Stark AD, Jordan S, Allers KA, Bertekap RL, Chen R, Mistry Kannan T, Molski TF, Yocca FD, Sharp T, Kikuchi T, Burris KD: Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT 2A receptors: functional receptor-binding and in vivo electrophysiological studies. Psychopharmacology (Berl). 2007 Feb;190(3):373-82. Epub 2006 Nov 25. Pubmed
  2. Meltzer HY: The role of serotonin in antipsychotic drug action. Neuropsychopharmacology. 1999 Aug;21(2 Suppl):106S-115S. Pubmed
  3. Meltzer HY: Role of serotonin in the action of atypical antipsychotic drugs. Clin Neurosci. 1995;3(2):64-75. Pubmed

15. Histamine H1 receptor

Pharmacological action: no
Actions: antagonist

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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system

Organism class: human
UniProt ID: P35367 Link_out
Gene: HRH1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. Arnt J: Differential effects of classical and newer antipsychotics on the hypermotility induced by two dose levels of D-amphetamine. Eur J Pharmacol. 1995 Sep 5;283(1-3):55-62. Pubmed

16. Alpha-1A adrenergic receptor

Pharmacological action: no
Actions: antagonist

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) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. 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

17. Alpha-1B adrenergic receptor

Pharmacological action: no
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P35368 Link_out
Gene: ADRA1B Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

18. Alpha-2A adrenergic receptor

Pharmacological action: no
Actions: antagonist

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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

Organism class: human
UniProt ID: P08913 Link_out
Gene: ADRA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

19. Alpha-2B adrenergic receptor

Pharmacological action: no
Actions: antagonist

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 > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol

Organism class: human
UniProt ID: P18089 Link_out
Gene: ADRA2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

20. Alpha-2C adrenergic receptor

Pharmacological action: no
Actions: antagonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins

Organism class: human
UniProt ID: P18825 Link_out
Gene: ADRA2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

21. Muscarinic acetylcholine receptor M1

Pharmacological action: no
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P11229 Link_out
Gene: CHRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

22. Muscarinic acetylcholine receptor M2

Pharmacological action: no
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition

Organism class: human
UniProt ID: P08172 Link_out
Gene: CHRM2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

23. Muscarinic acetylcholine receptor M3

Pharmacological action: no
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P20309 Link_out
Gene: CHRM3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

24. Muscarinic acetylcholine receptor M4

Pharmacological action: no
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase

Organism class: human
UniProt ID: P08173 Link_out
Gene: CHRM4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

25. Muscarinic acetylcholine receptor M5

Pharmacological action: no
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P08912 Link_out
Gene: CHRM5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  4. Nakamura H, Nakasa H, Ishii I, Ariyoshi N, Igarashi T, Ohmori S, Kitada M: Effects of endogenous steroids on CYP3A4-mediated drug metabolism by human liver microsomes. Drug Metab Dispos. 2002 May;30(5):534-40. Pubmed

2. Cytochrome P450 3A5

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 3A7

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:02

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.