Identification

Name
Chlorpromazine
Accession Number
DB00477  (APRD00482)
Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Description

The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class, chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup.

Structure
Thumb
Synonyms
  • 3-(2-chloro-10H-phenothiazin-10-yl)-N,N-dimethyl-1-propanamine
  • 3-(2-chlorophenothiazin-10-yl)-N,N-dimethyl-propan-1-amine
  • Chlorpromazinum
  • Clorpromazina
  • CPZ
  • N-(3-dimethylaminopropyl)-3-chlorophenothiazine
External IDs
J2.794D / NSC-167745 / NSC-226514
Product Ingredients
IngredientUNIICASInChI Key
Chlorpromazine hydrochloride9WP59609J669-09-0FBSMERQALIEGJT-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo ChlorpromazineTablet111.4 mgOralApotex Corporation1976-12-312011-08-05Canada
Apo ChlorpromazineTablet27.9 mgOralApotex Corporation1976-12-312011-08-05Canada
Apo ChlorpromazineTablet55.7 mgOralApotex Corporation1976-12-312011-08-05Canada
Chlorprom Tab 100mgTablet111.6 mgOralIcn Pharmaceuticals1962-12-311998-08-13Canada
Chlorprom Tab 25mgTablet27.9 mgOralIcn Pharmaceuticals1974-12-311998-08-13Canada
Chlorprom Tab 50mgTablet55.8 mgOralIcn Pharmaceuticals1962-12-311998-08-13Canada
Chlorpromanyl 20 SyrSolution / drops22.2 mgOralTechnilab Pharma Inc.1983-12-312004-08-03Canada
Chlorpromanyl 40 Drops Syr 44.5mg/mlSyrup44.5 mgOralTechnilab Pharma Inc.1986-12-312006-07-28Canada
Chlorpromazine HCl Inj 25mg/ml USPLiquid25 mgIntramuscular; IntravenousMylan Pharmaceuticals1994-12-312015-11-03Canada
Chlorpromazine HCl Inj 27.9mg/mlLiquid27.9 mgIntramuscular; IntravenousDavid Bull Laboratories (Pty) Ltd.1985-12-311996-09-10Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ChlorpromazineTablet, film coated50 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs1973-01-03Not applicableUs
ChlorpromazineTablet, film coated25 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs1973-01-03Not applicableUs
ChlorpromazineTablet, film coated100 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs1973-01-03Not applicableUs00781 1718 01 nlmimage10 7d04bef5
Chlorpromazine HydrochlorideTablet, film coated25 mg/1OralPhysicians Total Care, Inc.1973-01-03Not applicableUs
Chlorpromazine HydrochlorideTablet, sugar coated100 mg/1OralClinical Solutions Wholsesale1974-07-092017-06-15Us58118 004420180913 8702 1adu9ml
Chlorpromazine HydrochlorideTablet, sugar coated10 mg/1OralSandoz1974-07-09Not applicableUs
Chlorpromazine HydrochlorideTablet, film coated10 mg/1OralAmneal Pharmaceuticals LLC2018-09-12Not applicableUs
Chlorpromazine HydrochlorideTablet, sugar coated100 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs1974-07-09Not applicableUs00781 5916 01 nlmimage10 7a48bd05
Chlorpromazine HydrochlorideTablet, sugar coated100 mg/1OralA-S Medication Solutions2011-08-03Not applicableUs
Chlorpromazine HydrochlorideTablet, sugar coated50 mg/1OralMylan Institutional Inc.1994-11-23Not applicableUs
International/Other Brands
Aminazine / Chlorderazin / Chloropromazine / Chlorpromados / Chlorpromanyl (Technilab (Canada)) / Contomin / Largactil (Specia) / Thorazine (GlaxoSmithKline)
Categories
UNII
U42B7VYA4P
CAS number
50-53-3
Weight
Average: 318.864
Monoisotopic: 318.095747015
Chemical Formula
C17H19ClN2S
InChI Key
ZPEIMTDSQAKGNT-UHFFFAOYSA-N
InChI
InChI=1S/C17H19ClN2S/c1-19(2)10-5-11-20-14-6-3-4-7-16(14)21-17-9-8-13(18)12-15(17)20/h3-4,6-9,12H,5,10-11H2,1-2H3
IUPAC Name
[3-(2-chloro-10H-phenothiazin-10-yl)propyl]dimethylamine
SMILES
CN(C)CCCN1C2=CC=CC=C2SC2=C1C=C(Cl)C=C2

Pharmacology

Indication

For the treatment of schizophrenia; to control nausea and vomiting; for relief of restlessness and apprehension before surgery; for acute intermittent porphyria; as an adjunct in the treatment of tetanus; to control the manifestations of the manic type of manic-depressive illness; for relief of intractable hiccups; for the treatment of severe behavioral problems in children (1 to 12 years of age) marked by combativeness and/or explosive hyperexcitable behavior (out of proportion to immediate provocations), and in the short-term treatment of hyperactive children who show excessive motor activity with accompanying conduct disorders consisting of some or all of the following symptoms: impulsivity, difficulty sustaining attention, aggressivity, mood lability, and poor frustration tolerance.

Associated Conditions
Pharmacodynamics

Chlorpromazine is a psychotropic agent indicated for the treatment of schizophrenia. It also exerts sedative and antiemetic activity. Chlorpromazine has actions at all levels of the central nervous system-primarily at subcortical levels-as well as on multiple organ systems. Chlorpromazine has strong antiadrenergic and weaker peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity.

Mechanism of action

Chlorpromazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects). Additionally, Chlorpromazine is a weak presynaptic inhibitor of Dopamine reuptake, which may lead to (mild) antidepressive and antiparkinsonian effects. This action could also account for psychomotor agitation and amplification of psychosis (very rarely noted in clinical use).

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
AD(1A) dopamine receptor
antagonist
Human
A5-hydroxytryptamine receptor 1A
antagonist
Human
A5-hydroxytryptamine receptor 2A
antagonist
Human
AAlpha-1A adrenergic receptor
antagonist
Human
AAlpha-1B adrenergic receptor
antagonist
Human
AHistamine H1 receptor
antagonist
Human
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Human
UD(1) dopamine receptor
inhibitor
Human
UD(3) dopamine receptor
inhibitor
Human
UD(4) dopamine receptor
binder
Human
UD(1B) dopamine receptor
inhibitor
Human
U5-hydroxytryptamine receptor 2C
binder
Human
U5-hydroxytryptamine 2 receptor
binder
Human
UAlpha-1 adrenergic receptors
inhibitor
Human
UAlpha-2 adrenergic receptors
inhibitor
Human
UMuscarinic acetylcholine receptor M1
antagonist
Human
UMuscarinic acetylcholine receptor M3
antagonist
Human
USphingomyelin phosphodiesterase
inhibitor
Human
UCalmodulin
inhibitor
Human
Ualpha1-acid glycoprotein
binder
Human
U5-hydroxytryptamine receptor 6
binder
Human
U5-hydroxytryptamine receptor 7
binder
Human
UHistamine H4 receptor
binder
Human
Absorption

Readily absorbed from the GI tract. Bioavailability varies due to first-pass metabolism by the liver.

Volume of distribution
  • 20 L/kg
Protein binding

> 90% to plasma proteins, primarily albumin

Metabolism

Extensively metabolized in the liver and kidneys. It is extensively metabolized by cytochrome P450 isozymes CYP2D6 (major pathway), CYP1A2 and CYP3A4. Approximately 10 to 12 major metabolite have been identified. Hydroxylation at positions 3 and 7 of the phenothiazine nucleus and the N-dimethylaminopropyl side chain undergoes demethylation and is also metabolized to an N-oxide. In urine, 20% of chlopromazine and its metabolites are excreted unconjugated in the urine as unchanged drug, demonomethylchlorpromazine, dedimethylchlorpromazine, their sulfoxide metabolites, and chlorpromazine-N-oxide. The remaining 80% consists of conjugated metabolites, principally O-glucuronides and small amounts of ethereal sulfates of the mono- and dihydroxy-derivatives of chlorpromazine and their sulfoxide metabolites. The major metabolites are the monoglucuronide of N-dedimethylchlorpromazine and 7-hydroxychlorpromazine. Approximately 37% of the administered dose of chlorpromazine is excreted in urine.

Route of elimination

Kidneys, ~ 37% excreted in urine

Half life

~ 30 hours

Clearance
Not Available
Toxicity

Agitation, coma, convulsions, difficulty breathing, difficulty swallowing, dry mouth, extreme sleepiness, fever, intestinal blockage, irregular heart rate, low blood pressure, restlessness

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Chlorpromazine.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Chlorpromazine is combined with (S)-Warfarin.
1,10-PhenanthrolineThe therapeutic efficacy of Chlorpromazine can be decreased when used in combination with 1,10-Phenanthroline.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Chlorpromazine.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Chlorpromazine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Chlorpromazine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Chlorpromazine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Chlorpromazine is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Chlorpromazine.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Chlorpromazine.
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.

References

Synthesis Reference

Charpentier, P.; U S . Patent 2,645,640; July 14, 1953; assigned to Societe des Usines Chimiques Rhone-Poulenc, France.

US2645640
General References
  1. Leucht S, Wahlbeck K, Hamann J, Kissling W: New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet. 2003 May 10;361(9369):1581-9. [PubMed:12747876]
External Links
Human Metabolome Database
HMDB0014620
KEGG Drug
D00270
KEGG Compound
C06906
PubChem Compound
2726
PubChem Substance
46508395
ChemSpider
2625
BindingDB
50001888
ChEBI
3647
ChEMBL
CHEMBL71
Therapeutic Targets Database
DAP000374
PharmGKB
PA448964
IUPHAR
83
Guide to Pharmacology
GtP Drug Page
HET
Z80
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Chlorpromazine
ATC Codes
N05AA01 — Chlorpromazine
AHFS Codes
  • 28:16.08.24 — Phenothiazines
PDB Entries
3apx / 3lk0 / 4ma8 / 5g08 / 5lg3 / 5nuj / 5nuk / 5num / 5nun
MSDS
Download (75.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceAcute Intermittent Porphyria (AIP) / Adjunct in the Treatment of Tetanus / Anti-Psychotic / Control Manifestations of the Manic Type of Mani-depressive Illness / Control Nausea and Vomiting / Management of Manifestations of Psychotic Disorders / Relief of Intractable Hiccups / Relief of Restlessness and Apprehension Before Surgery / Treatment of Schizophrenia1
1, 2Not Yet RecruitingTreatmentMetastatic Carcinoma of the Cervix1
2Active Not RecruitingTreatmentAdenocarcinoma of the Lung / Adenosquamous Cell Lung Cancer / Adenosquamous Lung Carcinoma / Bronchoalveolar Cell Lung Cancer / Large Cell Lung Cancer / Large Cell Lung Carcinoma / Minimally Invasive Lung Adenocarcinoma / Squamous Cell Carcinoma of Lung / Squamous Cell Lung Carcinoma / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIA Non-Small Cell Lung Cancer AJCC v7 / Stage IIIb Non-small Cell Lung Cancer / Stage IIIB Non-Small Cell Lung Cancer AJCC v71
2Active Not RecruitingTreatmentClear Cell Renal Cell Carcinoma / Renal Cell Cancer, Recurrent / Renal Cell Carcinoma Recurrent / Stage IV Renal Cell Cancer / Stage IV Renal Cell Cancer AJCC V71
2Active Not RecruitingTreatmentGastrin-Producing Neuroendocrine Tumor / Malignant Pancreatic Gastrinoma / Malignant Pancreatic Glucagonoma / Malignant Pancreatic Insulinoma / Malignant Pancreatic Somatostatinoma / Pancreatic Alpha Cell Adenoma / Pancreatic Beta Cell Adenoma / Pancreatic Delta Cell Adenoma / Pancreatic G-Cell Adenoma / Pancreatic Gastrinoma / Pancreatic Glucagonoma / Pancreatic Insulinoma / Pancreatic Neuroendocrine Tumor G1 / Pancreatic Neuroendocrine Tumor G2 / Pancreatic Polypeptide Tumor / Pancreatic Vipoma / Recurrent Pancreatic Carcinoma / Recurrent Pancreatic Neuroendocrine Carcinoma / Somatostatin-Producing Neuroendocrine Tumor / Stage III Pancreatic Cancer / Stage IV Pancreatic Cancer1
2Active Not RecruitingTreatmentRectal Adenocarcinoma / Stage II Rectal Cancer / Stage II Rectal Cancer AJCC v7 / Stage III Rectal Cancer / Stage III Rectal Cancer AJCC v71
2, 3RecruitingTreatmentMalignant Neoplasms of Independent (Primary) Multiple Sites1
3Active Not RecruitingTreatmentAtypical Carcinoid Tumor / Carcinoid Tumors / Colorectal Neuroendocrine Tumor G1 / Gastric Neuroendocrine Tumor G1 / Neuroendocrine Carcinomas / Neuroendocrine Neoplasms1
3CompletedTreatmentDrug withdrawal syndrome neonatal1
3CompletedTreatmentSchizophrenic Disorders1
3RecruitingTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cancer1
3RecruitingTreatmentCervical Cancers1
3Unknown StatusTreatmentPsychosis Nos/Other1
4CompletedTreatmentBipolar Disorder (BD) / Schizoaffective Disorders1
4CompletedTreatmentSchizophrenic Disorders1
4RecruitingTreatmentAcute Agitation / Aggressive Behavior / Psychiatric Emergency1
4TerminatedTreatmentSchizophrenic Disorders1
Not AvailableCompletedNot AvailableBipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableSchizophrenic Disorders1
Not AvailableCompletedSupportive CareBlind Painful Eye / Control of Pain Through Drug Injection / Refractory Glaucoma1

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline
  • Actavis mid atlantic llc
  • Pharmaceutical assoc inc div beach products
  • Wockhardt eu operations (swiss) ag
  • Roxane laboratories inc
  • Sandoz inc
  • Abraxis pharmaceutical products
  • Baxter healthcare corp anesthesia and critical care
  • Marsam pharmaceuticals llc
  • Watson laboratories inc
  • Wyeth ayerst laboratories
  • Alpharma us pharmaceuticals division
  • Abbott laboratories pharmaceutical products div
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Kv pharmaceutical co
  • Lederle laboratories div american cyanamid co
  • Purepac pharmaceutical co
  • Private formulations inc
  • Usl pharma inc
  • Vangard laboratories inc div midway medical co
  • West ward pharmaceutical corp
  • Parke davis div warner lambert co
Packagers
  • Amerisource Health Services Corp.
  • Baxter International Inc.
  • Cardinal Health
  • Comprehensive Consultant Services Inc.
  • Coupler Enterprises Inc.
  • Heartland Repack Services LLC
  • Innovative Manufacturing and Distribution Services Inc.
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Qualitest
  • Remedy Repack
  • Sandoz
  • Tya Pharmaceuticals
  • UDL Laboratories
  • United Research Laboratories Inc.
  • USL Pharma Inc.
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
TabletOral111.4 mg
TabletOral55.7 mg
TabletOral111.6 mg
TabletOral27.9 mg
TabletOral55.8 mg
Solution / dropsOral22.2 mg
SyrupOral44.5 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral50 mg/1
LiquidIntramuscular; Intravenous25 mg
SolutionIntramuscular; Intravenous25 mg
InjectionIntramuscular25 mg/1mL
TabletOral10 mg/1
TabletOral100 mg/1
TabletOral200 mg/1
TabletOral25 mg/1
TabletOral50 mg/1
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral25 mg/1
Tablet, sugar coatedOral10 mg/1
Tablet, sugar coatedOral100 mg/1
Tablet, sugar coatedOral200 mg/1
Tablet, sugar coatedOral25 mg/1
Tablet, sugar coatedOral50 mg/1
LiquidIntramuscular; Intravenous27.9 mg
TabletOral25 mg
TabletOral50 mg
LiquidOral100 mg
LiquidOral25 mg
SolutionIntramuscular; Intravenous50 mg
Solution / dropsOral40 mg
SuppositoryRectal100 mg
TabletOral223.2 mg
TabletOral11.16 mg
TabletOral100 mg
TabletOral25.0 mg
TabletOral50.0 mg
Injection, solutionIntramuscular25 mg/1mL
SuppositoryRectal100 mg/1
SuppositoryRectal25 mg/1
SyrupOral10 mg/5mL
Tablet, coatedOral10 mg/1
Tablet, coatedOral100 mg/1
Tablet, coatedOral200 mg/1
Tablet, coatedOral25 mg/1
Tablet, coatedOral50 mg/1
Prices
Unit descriptionCostUnit
Chlorpromazine 25 mg/ml amp8.04USD ml
ChlorproMAZINE HCl 200 mg tablet1.19USD tablet
Chlorpromazine 200 mg tablet1.05USD tablet
ChlorproMAZINE HCl 100 mg tablet0.84USD tablet
ChlorproMAZINE HCl 50 mg tablet0.73USD tablet
ChlorproMAZINE HCl 25 mg tablet0.55USD tablet
Chlorpromazine 100 mg tablet0.39USD tablet
ChlorproMAZINE HCl 10 mg tablet0.37USD tablet
Chlorpromazine 10 mg tablet0.32USD tablet
Chlorpromazine 50 mg tablet0.3USD tablet
Chlorpromazine 25 mg tablet0.17USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)177-178Charpentier, P.; U S . Patent 2,645,640; July 14, 1953; assigned to Societe des Usines Chimiques Rhone-Poulenc, France
boiling point (°C)200-205 °C at 8.00E-01 mm HgPhysProp
water solubility2.55 mg/L (at 24 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP5.41AVDEEF,A (1995)
logS-5.01ADME Research, USCD
Caco2 permeability-4.7ADME Research, USCD
pKa9.3 (at 25 °C)HANSCH,C & LEO,AJ (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.00417 mg/mLALOGPS
logP5.18ALOGPS
logP4.54ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)9.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity93.76 m3·mol-1ChemAxon
Polarizability35.1 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9757
Blood Brain Barrier+0.9795
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.787
P-glycoprotein inhibitor IInhibitor0.7164
P-glycoprotein inhibitor IIInhibitor0.8387
Renal organic cation transporterInhibitor0.7557
CYP450 2C9 substrateNon-substrate0.7617
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.6477
CYP450 1A2 substrateInhibitor0.9305
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.9422
CYP450 2C19 inhibitorInhibitor0.5512
CYP450 3A4 inhibitorNon-inhibitor0.9375
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6601
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9309
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.3196 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9536
hERG inhibition (predictor II)Inhibitor0.787
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.36 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0a4r-9053000000-9e1cc1d4fc6be5bc73b8
GC-MS Spectrum - CI-BGC-MSsplash10-014i-2019000000-54e008f9fc11d7f45b68
GC-MS Spectrum - CI-BGC-MSsplash10-000i-9070000000-9bbe6c5123c891b9489b
Mass Spectrum (Electron Ionization)MSsplash10-0a4i-9231000000-ed14fee152701eacf689
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0019000000-0028b3984b4c35e44def
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0002-0090000000-800bf68c2158920c3f30
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03dj-0090000000-649e773296a3ecec2b04
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-0190000000-7404aac4e28621b4f60a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-01b9-0019000000-993566c51e802e754da2

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazines
Sub Class
Phenothiazines
Direct Parent
Phenothiazines
Alternative Parents
Alkyldiarylamines / Diarylthioethers / Benzenoids / Aryl chlorides / 1,4-thiazines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
Phenothiazine / Alkyldiarylamine / Diarylthioether / Aryl thioether / Tertiary aliphatic/aromatic amine / Para-thiazine / Aryl chloride / Aryl halide / Benzenoid / Tertiary aliphatic amine
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, tertiary amine, organochlorine compound (CHEBI:3647)

Targets

Details
1. D(2) dopamine receptor
Kind
Protein
Organism
Human
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
  1. Oades RD, Rao ML, Bender S, Sartory G, Muller BW: Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy. Behav Pharmacol. 2000 Jun;11(3-4):317-30. [PubMed:11103886]
  2. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed:11873706]
  3. Wu S, Xing Q, Gao R, Li X, Gu N, Feng G, He L: Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neurosci Lett. 2005 Mar 7;376(1):1-4. Epub 2004 Dec 2. [PubMed:15694263]
  4. Wu SN, Gao R, Xing QH, Li HF, Shen YF, Gu NF, Feng GY, He L: Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients. Acta Pharmacol Sin. 2006 Aug;27(8):966-70. [PubMed:16867246]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  6. Seeman P: Dopamine D2 receptors as treatment targets in schizophrenia. Clin Schizophr Relat Psychoses. 2010 Apr;4(1):56-73. doi: 10.3371/CSRP.4.1.5. [PubMed:20643630]
  7. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ Jr, Shen Y, Meltzer HY, Sibley DR: Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10. [PubMed:7908055]
  8. Roth BL, Tandra S, Burgess LH, Sibley DR, Meltzer HY: D4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs. Psychopharmacology (Berl). 1995 Aug;120(3):365-8. [PubMed:8524985]
Details
2. D(1A) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
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
  1. Kanba S, Suzuki E, Nomura S, Nakaki T, Yagi G, Asai M, Richelson E: Affinity of neuroleptics for D1 receptor of human brain striatum. J Psychiatry Neurosci. 1994 Jul;19(4):265-9. [PubMed:7918347]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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. 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
  1. Cosi C, Koek W: Agonist, antagonist, and inverse agonist properties of antipsychotics at human recombinant 5-HT(1A) receptors expressed in HeLa cells. Eur J Pharmacol. 2001 Dec 14;433(1):55-62. [PubMed:11755134]
  2. Newman-Tancredi A, Gavaudan S, Conte C, Chaput C, Touzard M, Verriele L, Audinot V, Millan MJ: Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study. Eur J Pharmacol. 1998 Aug 21;355(2-3):245-56. [PubMed:9760039]
Kind
Protein
Organism
Human
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
  1. Kusumi I, Takahashi Y, Suzuki K, Kameda K, Koyama T: Differential effects of subchronic treatments with atypical antipsychotic drugs on dopamine D2 and serotonin 5-HT2A receptors in the rat brain. J Neural Transm (Vienna). 2000;107(3):295-302. [PubMed:10821438]
  2. Yamada J, Sugimoto Y, Horisaka K: Serotonin2 (5-HT2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) inhibits chlorpromazine- and haloperidol-induced hypothermia in mice. Biol Pharm Bull. 1995 Nov;18(11):1580-3. [PubMed:8593484]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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
  1. Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. [PubMed:15695070]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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
  1. Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. [PubMed:15695070]
Details
7. Histamine H1 receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
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
  1. Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. [PubMed:2899826]
  2. Church MK, Young KD: The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine. Br J Pharmacol. 1983 Apr;78(4):671-9. [PubMed:6189542]
  3. Johnson HG, Miller MD: Inhibition of histamine release and ionophore-induced calcium flux in rat mast cells by lidocaine and chlorpromazine. Agents Actions. 1979 Aug;9(3):239-43. [PubMed:91313]
  4. Palmer GC, Wagner HR, Palmer SJ, Manian AA: Histamine-, norepinephrine-, and dopamine-sensitive central adenylate cyclases: effects of chlorpromazine derivatives and butaclamol. Arch Int Pharmacodyn Ther. 1978 Jun;233(2):314-25. [PubMed:687395]
  5. Ruffolo RR, Patil PN: Kinetics of blockade of different receptors by chlorpromazine in rabbit stomach strips. Eur J Pharmacol. 1978 Mar 15;48(2):151-7. [PubMed:25190]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Thomas D, Wu K, Kathofer S, Katus HA, Schoels W, Kiehn J, Karle CA: The antipsychotic drug chlorpromazine inhibits HERG potassium channels. Br J Pharmacol. 2003 Jun;139(3):567-74. [PubMed:12788816]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.

Components:
References
  1. Seeman P, Van Tol HH: Dopamine receptor pharmacology. Curr Opin Neurol Neurosurg. 1993 Aug;6(4):602-8. [PubMed:8104554]
Details
10. D(3) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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
  1. Freedman SB, Patel S, Marwood R, Emms F, Seabrook GR, Knowles MR, McAllister G: Expression and pharmacological characterization of the human D3 dopamine receptor. J Pharmacol Exp Ther. 1994 Jan;268(1):417-26. [PubMed:8301582]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
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
  1. Roth BL, Tandra S, Burgess LH, Sibley DR, Meltzer HY: D4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs. Psychopharmacology (Berl). 1995 Aug;120(3):365-8. [PubMed:8524985]
Details
12. D(1B) dopamine receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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
  1. Seeman P, Van Tol HH: Dopamine receptor pharmacology. Curr Opin Neurol Neurosurg. 1993 Aug;6(4):602-8. [PubMed:8104554]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
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
  1. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ Jr, Shen Y, Meltzer HY, Sibley DR: Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10. [PubMed:7908055]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Binder
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...

Components:
References
  1. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ Jr, Shen Y, Meltzer HY, Sibley DR: Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10. [PubMed:7908055]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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...

Components:
References
  1. Huerta-Bahena J, Villalobos-Molina R, Garcia-Sainz JA: Trifluoperazine and chlorpromazine antagonize alpha 1- but not alpha2- adrenergic effects. Mol Pharmacol. 1983 Jan;23(1):67-70. [PubMed:6135146]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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...

Components:
References
  1. Bylund DB, Ray-Prenger C, Murphy TJ: Alpha-2A and alpha-2B adrenergic receptor subtypes: antagonist binding in tissues and cell lines containing only one subtype. J Pharmacol Exp Ther. 1988 May;245(2):600-7. [PubMed:2835476]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
  1. Davies MA, Compton-Toth BA, Hufeisen SJ, Meltzer HY, Roth BL: The highly efficacious actions of N-desmethylclozapine at muscarinic receptors are unique and not a common property of either typical or atypical antipsychotic drugs: is M1 agonism a pre-requisite for mimicking clozapine's actions? Psychopharmacology (Berl). 2005 Apr;178(4):451-60. Epub 2004 Oct 13. [PubMed:15765260]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
  1. Davies MA, Compton-Toth BA, Hufeisen SJ, Meltzer HY, Roth BL: The highly efficacious actions of N-desmethylclozapine at muscarinic receptors are unique and not a common property of either typical or atypical antipsychotic drugs: is M1 agonism a pre-requisite for mimicking clozapine's actions? Psychopharmacology (Berl). 2005 Apr;178(4):451-60. Epub 2004 Oct 13. [PubMed:15765260]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sphingomyelin phosphodiesterase activity
Specific Function
Converts sphingomyelin to ceramide. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol. Isoform 2 and isoform 3 have lost catalytic ac...
Gene Name
SMPD1
Uniprot ID
P17405
Uniprot Name
Sphingomyelin phosphodiesterase
Molecular Weight
69751.3 Da
References
  1. Yoshida Y, Arimoto K, Sato M, Sakuragawa N, Arima M, Satoyoshi E: Reduction of acid sphingomyelinase activity in human fibroblasts induced by AY-9944 and other cationic amphiphilic drugs. J Biochem. 1985 Dec;98(6):1669-79. [PubMed:2419314]
Details
20. Calmodulin
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Titin binding
Specific Function
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number...
Gene Name
CALM1
Uniprot ID
P0DP23
Uniprot Name
Calmodulin
Molecular Weight
16837.47 Da
References
  1. Marshak DR, Lukas TJ, Watterson DM: Drug-protein interactions: binding of chlorpromazine to calmodulin, calmodulin fragments, and related calcium binding proteins. Biochemistry. 1985 Jan 1;24(1):144-50. [PubMed:2986673]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Binder
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...

Components:
References
  1. Herve F, Duche JC, d'Athis P, Marche C, Barre J, Tillement JP: Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. [PubMed:8946472]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
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
  1. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ Jr, Shen Y, Meltzer HY, Sibley DR: Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10. [PubMed:7908055]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
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
  1. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ Jr, Shen Y, Meltzer HY, Sibley DR: Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10. [PubMed:7908055]
Details
24. Histamine H4 receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Histamine receptor activity
Specific Function
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agoni...
Gene Name
HRH4
Uniprot ID
Q9H3N8
Uniprot Name
Histamine H4 receptor
Molecular Weight
44495.375 Da
References
  1. Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O'Dowd BF: Discovery of a novel member of the histamine receptor family. Mol Pharmacol. 2001 Mar;59(3):427-33. [PubMed:11179435]

Enzymes

Details
1. Cytochrome P450 2D6
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Micallef J, Fakra E, Blin O: [Use of antidepressant drugs in schizophrenic patients with depression]. Encephale. 2006 Mar-Apr;32(2 Pt 1):263-9. [PubMed:16910628]
  2. Otani K, Aoshima T: Pharmacogenetics of classical and new antipsychotic drugs. Ther Drug Monit. 2000 Feb;22(1):118-21. [PubMed:10688273]
  3. Yoshii K, Kobayashi K, Tsumuji M, Tani M, Shimada N, Chiba K: Identification of human cytochrome P450 isoforms involved in the 7-hydroxylation of chlorpromazine by human liver microsomes. Life Sci. 2000;67(2):175-84. [PubMed:10901285]
  4. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  5. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  6. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Yoshii K, Kobayashi K, Tsumuji M, Tani M, Shimada N, Chiba K: Identification of human cytochrome P450 isoforms involved in the 7-hydroxylation of chlorpromazine by human liver microsomes. Life Sci. 2000;67(2):175-84. [PubMed:10901285]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  4. Chlorpromazine Prescribing Info [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  2. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Tassaneeyakul W, Birkett DJ, Miners JO: Inhibition of human hepatic cytochrome P4502E1 by azole antifungals, CNS-active drugs and non-steroidal anti-inflammatory agents. Xenobiotica. 1998 Mar;28(3):293-301. [PubMed:9574817]
Kind
Protein
Organism
Human
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
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  2. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Nasello AG, Gidali D, Felicio LF: A comparative study of the anticholinesterase activity of several antipsychotic agents. Pharmacol Biochem Behav. 2003 Jul;75(4):895-901. [PubMed:12957233]
  2. Muraoka S, Miura T: Inactivation of cholinesterase induced by chlorpromazine cation radicals. Pharmacol Toxicol. 2003 Feb;92(2):100-4. [PubMed:12747580]
  3. Spinedi A, Pacini L, Limatola C, Luly P, Farias RN: A study of human erythrocyte acetylcholinesterase inhibition by chlorpromazine. Biochem J. 1991 Sep 1;278 ( Pt 2):461-3. [PubMed:1654884]

Carriers

Details
1. Serum albumin
Kind
Protein
Organism
Human
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
  1. Kitamura K, Omran AA, Nagata C, Kamijima Y, Tanaka R, Takegami S, Kitade T: Effects of inorganic ions on the binding of triflupromazine and chlorpromazine to bovine serum albumin studied by spectrometric methods. Chem Pharm Bull (Tokyo). 2006 Jul;54(7):972-6. [PubMed:16819214]
  2. Rukhadze MD, Bezarashvili GS, Sidamonidze NS, Tsagareli SK: Investigation of binding process of chlorpromazine to bovine serum albumin by means of passive and active experiments. Biomed Chromatogr. 2001 Oct;15(6):365-73. [PubMed:11559920]
  3. Silva D, Cortez CM, Louro SR: Quenching of the intrinsic fluorescence of bovine serum albumin by chlorpromazine and hemin. Braz J Med Biol Res. 2004 Jul;37(7):963-8. Epub 2004 Jun 22. [PubMed:15264002]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674]
  2. Boulton DW, DeVane CL, Liston HL, Markowitz JS: In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. Life Sci. 2002 May 31;71(2):163-9. [PubMed:12031686]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. [PubMed:12606755]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Wilson A. (2016). New horizons in predictive drug metabolism and pharmacokinetics. The Royal Society of Chemistry. [ISBN:978-1-84973-828-6]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:42