Identification
- Summary
Chlorprothixene is a thioxanthene antipsychotic.
- Generic Name
- Chlorprothixene
- DrugBank Accession Number
- DB01239
- Background
Chlorprothixene is a typical antipsychotic drug of the thioxanthene (tricyclic) class. Chlorprothixene exerts strong blocking effects by blocking the 5-HT2 D1, D2, D3, histamine H1, muscarinic and alpha1 adrenergic receptors.
- Type
- Small Molecule
- Groups
- Approved, Experimental, Investigational, Withdrawn
- Structure
Structure for Chlorprothixene (DB01239)
- Weight
- Average: 315.86
Monoisotopic: 315.0848485 - Chemical Formula
- C18H18ClNS
- Synonyms
- Alpha-Chlorprothixene
- Chlorprothixen
- Chlorprothixene
- Chlorprothixine
- Chlorprotixen
- Chlorprotixene
- Chlorprotixine
- Chlothixen
Pharmacology
- Indication
For treatment of psychotic disorders (e.g. schizophrenia) and of acute mania occuring as part of bipolar disorders.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Psychosis •••••••••••• •••••• Treatment of Schizophrenia •••••••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Chlorprothixene is a typical antipsychotic drug of the thioxanthine class. It has a low antipsychotic potency (half to 2/3 of chlorpromazine). Chlorprothixene has not thoroughly demonstrated an antidepressant or analgesic effect but it has demonstrated antiemetic effects. It is used in the treatment of nervous, mental, and emotional conditions. Improvement in such conditions is thought to result from the effect of the medicine on nerve pathways in specific areas of the brain. Chlorprothixene has a similar side effect profile to chlorpromazine, though allergic side effects and liver damage are less frequent.
- Mechanism of action
Chlorprothixene blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.
Target Actions Organism ADopamine D2 receptor antagonistHumans ADopamine D1 receptor antagonistHumans ADopamine D3 receptor antagonistHumans A5-hydroxytryptamine receptor 2A antagonistHumans AHistamine H1 receptor antagonistHumans ASerotonin Receptors inhibitorHumans NMuscarinic acetylcholine receptor M1 antagonistHumans NMuscarinic acetylcholine receptor M2 antagonistHumans NMuscarinic acetylcholine receptor M3 antagonistHumans NMuscarinic acetylcholine receptor M4 antagonistHumans NMuscarinic acetylcholine receptor M5 antagonistHumans - Absorption
Incomplete bioavailability.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hepatic
- Route of elimination
Not Available
- Half-life
8 to 12 hours
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Symptoms of overdose include difficulty in breathing (severe), dizziness (severe), drowsiness (severe), muscle trembling, jerking, stiffness, or uncontrolled movements (severe), small pupils, unusual excitement, and unusual tiredness or weakness (severe).
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Chlorprothixene is combined with 1,2-Benzodiazepine. Acenocoumarol The risk or severity of adverse effects can be increased when Chlorprothixene is combined with Acenocoumarol. Acetazolamide The risk or severity of CNS depression can be increased when Acetazolamide is combined with Chlorprothixene. Acetophenazine The risk or severity of CNS depression can be increased when Acetophenazine is combined with Chlorprothixene. Aclidinium The risk or severity of adverse effects can be increased when Chlorprothixene is combined with Aclidinium. - Food Interactions
- Avoid alcohol.
- Take with food. Food reduces irritation.
Products
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Ingredient UNII CAS InChI Key Chlorprothixene hydrochloride 268KCR965N 6469-93-8 YWKRLOSRDGPEJR-KIUKIJHYSA-N - International/Other Brands
- Clothixen (Yoshitomi) / Cloxan (Orion) / Taractan (Roche)
Categories
- ATC Codes
- N05AF03 — Chlorprothixene
- Drug Categories
- Agents producing tachycardia
- Anticholinergic Agents
- Antidepressive Agents
- Antipsychotic Agents
- Antipsychotic Agents (First Generation [Typical])
- Central Nervous System Agents
- Central Nervous System Depressants
- Dopamine Agents
- Dopamine Antagonists
- Dopamine D2 Receptor Antagonists
- Heterocyclic Compounds, Fused-Ring
- Histamine Antagonists
- Histamine H1 Antagonists
- Muscarinic Antagonists
- Nervous System
- Neurotoxic agents
- Neurotransmitter Agents
- P-glycoprotein inhibitors
- Potential QTc-Prolonging Agents
- Psycholeptics
- Psychotropic Drugs
- QTc Prolonging Agents
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin Agents
- Serotonin Receptor Antagonists
- Sulfur Compounds
- Thioxanthene Derivatives
- Thioxanthenes
- Tranquilizing Agents
- Xanthenes
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 9S7OD60EWP
- CAS number
- 113-59-7
- InChI Key
- WSPOMRSOLSGNFJ-AUWJEWJLSA-N
- InChI
- InChI=1S/C18H18ClNS/c1-20(2)11-5-7-14-15-6-3-4-8-17(15)21-18-10-9-13(19)12-16(14)18/h3-4,6-10,12H,5,11H2,1-2H3/b14-7-
- IUPAC Name
- {3-[(9Z)-2-chloro-9H-thioxanthen-9-ylidene]propyl}dimethylamine
- SMILES
- CN(C)CC\C=C1\C2=CC=CC=C2SC2=CC=C(Cl)C=C12
References
- Synthesis Reference
Sprague, J.M. and Engelhardt, E.L.; US. Patent 2,951,082; August 30, 1960; assigned to Merck & Co., Inc. Schlapfer, R. and Spiegelberg, H.; US. Patent 3,115,502; December 24,1963; assigned to Hoffmann-LaRoche Inc.
US3046283- General References
- Not Available
- External Links
- KEGG Drug
- D00790
- KEGG Compound
- C07953
- PubChem Compound
- 667466
- PubChem Substance
- 46508957
- ChemSpider
- 580849
- BindingDB
- 50240514
- 2406
- ChEBI
- 50931
- ChEMBL
- CHEMBL908
- ZINC
- ZINC000000001137
- Therapeutic Targets Database
- DAP000833
- PharmGKB
- PA164781400
- Wikipedia
- Chlorprothixene
- MSDS
- Download (63.3 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Terminated Treatment Anxiety Disorders / Dementia / Depression / Psychosomatic Disorders / Schizophrenia 1 Not Available Completed Not Available Bipolar Disorder (BD) / Psychosis / Schizoaffective Disorders / Schizophrenia / Type 2 Diabetes Mellitus 1 Not Available Recruiting Not Available Obesity, Morbid 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 15 mg/1 Tablet, film coated Oral 50 mg/1 Tablet, film coated Oral 90 mg/1 Tablet, film coated Oral 15 MG Tablet, film coated Oral 50 MG - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 153-154 Sprague, J.M. and Engelhardt, E.L.; US. Patent 2,951,082; August 30, 1960; assigned to Merck & Co., Inc. Schlapfer, R. and Spiegelberg, H.; US. Patent 3,115,502; December 24,1963; assigned to Hoffmann-LaRoche Inc. water solubility 0.295 mg/L Not Available logP 5.18 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.000366 mg/mL ALOGPS logP 5.42 ALOGPS logP 5.07 Chemaxon logS -5.9 ALOGPS pKa (Strongest Basic) 9.76 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 3.24 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 104.66 m3·mol-1 Chemaxon Polarizability 35.77 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9899 Blood Brain Barrier + 0.95 Caco-2 permeable + 0.7404 P-glycoprotein substrate Substrate 0.8042 P-glycoprotein inhibitor I Inhibitor 0.8407 P-glycoprotein inhibitor II Inhibitor 0.8884 Renal organic cation transporter Inhibitor 0.72 CYP450 2C9 substrate Non-substrate 0.7199 CYP450 2D6 substrate Substrate 0.6845 CYP450 3A4 substrate Substrate 0.7096 CYP450 1A2 substrate Inhibitor 0.9106 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8931 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.8308 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.768 Ames test Non AMES toxic 0.7084 Carcinogenicity Non-carcinogens 0.8714 Biodegradation Not ready biodegradable 0.9838 Rat acute toxicity 3.1665 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8117 hERG inhibition (predictor II) Inhibitor 0.7373
Spectra
- Mass Spec (NIST)
- Download (8.22 KB)
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-01b9-0059000000-42b939b1ca50abc0dc7f Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-0009000000-93ef2c8704ae801d71a5 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-2094000000-bbec5a732c2dec06b607 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-2069000000-66607713632d4be4377e Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-05g0-0090000000-5d056817edc427a9901e Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9010000000-1317deaef4a4eac32efa Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- 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
- Froimowitz M, Cody V: Biologically active conformers of phenothiazines and thioxanthenes. Further evidence for a ligand model of dopamine D2 receptor antagonists. J Med Chem. 1993 Jul 23;36(15):2219-27. [Article]
- Fux M, Belmaker RH: A controlled comparative study of chlorprothixene vs. haloperidol in chronic schizophrenia. Isr J Psychiatry Relat Sci. 1991;28(1):37-40. [Article]
- von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- Fux M, Belmaker RH: A controlled comparative study of chlorprothixene vs. haloperidol in chronic schizophrenia. Isr J Psychiatry Relat Sci. 1991;28(1):37-40. [Article]
- Kind
- Protein
- Organism
- Humans
- 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 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. [Article]
- 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. [Article]
- Fux M, Belmaker RH: A controlled comparative study of chlorprothixene vs. haloperidol in chronic schizophrenia. Isr J Psychiatry Relat Sci. 1991;28(1):37-40. [Article]
- 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
- Antkiewicz-Michaluk L: The influence of chronic treatment with antidepressant neuroleptics on the central serotonin system. Pol J Pharmacol Pharm. 1986 Jul-Aug;38(4):359-70. [Article]
- Wander TJ, Nelson A, Okazaki H, Richelson E: Antagonism by neuroleptics of serotonin 5-HT1A and 5-HT2 receptors of normal human brain in vitro. Eur J Pharmacol. 1987 Nov 10;143(2):279-82. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- Curator comments
- Some in vitro studies provide evidence of this target relationship, however, further research is warranted.
- 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
- Vasudevan SR, Moore JB, Schymura Y, Churchill GC: Shape-based reprofiling of FDA-approved drugs for the H(1) histamine receptor. J Med Chem. 2012 Aug 23;55(16):7054-60. doi: 10.1021/jm300671m. Epub 2012 Aug 6. [Article]
- Ding P, Yan X, Liu Z, Du J, Du Y, Lu Y, Wu D, Xu Y, Zhou H, Gu Q, Xu J: PTS: a pharmaceutical target seeker. Database (Oxford). 2017 Jan 1;2017. pii: 4781737. doi: 10.1093/database/bax095. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- Not all literature specifies the specificity of this drug for the serotonin receptor subtypes.
- 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...
Components:
References
- Drummond AH, Whigham KA, Prentice CR: Effects of chlorprothixene isomers on platelet 5-hydroxytryptamine receptors: evidence for different 5-hydroxytryptamine conformations at uptake and stimulatory sites. Eur J Pharmacol. 1976 Jun;37(2):385-8. doi: 10.1016/0014-2999(76)90047-9. [Article]
- 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
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- 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
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- 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
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- 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
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- 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
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- 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
- Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. [Article]
Drug created at June 13, 2005 13:24 / Updated at June 09, 2021 08:40