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Identification
NameChlorprothixene
Accession NumberDB01239  (APRD00718)
TypeSmall Molecule
GroupsApproved, Withdrawn
Description

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.

Structure
Thumb
Synonyms
Alpha-Chlorprothixene
Chlorprothixen
Chlorprothixine
Chlorprotixen
Chlorprotixene
Chlorprotixine
Chlothixen
External Identifiers Not Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
ClothixenYoshitomi
CloxanOrion
TaractanRoche
Brand mixturesNot Available
SaltsNot Available
Categories
UNII9S7OD60EWP
CAS number113-59-7
WeightAverage: 315.86
Monoisotopic: 315.084847978
Chemical FormulaC18H18ClNS
InChI KeyInChIKey=WSPOMRSOLSGNFJ-VGOFMYFVSA-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-(2-chloro-9H-thioxanthen-9-ylidene)propyl]dimethylamine
SMILES
[H]C(CCN(C)C)=C1C2=CC(Cl)=CC=C2SC2=C1C=CC=C2
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as thioxanthenes. These are organic polycyclic compounds containing a thioxanthene moiety, which is an aromatic tricycle derived from xanthene by replacing the oxygen atom with a sulfur atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiopyrans
Sub Class1-benzothiopyrans
Direct ParentThioxanthenes
Alternative Parents
Substituents
  • Thioxanthene
  • Diarylthioether
  • Chlorobenzene
  • Benzenoid
  • Aryl halide
  • Aryl chloride
  • Tertiary aliphatic amine
  • Tertiary amine
  • Thioether
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor treatment of psychotic disorders (e.g. schizophrenia) and of acute mania occuring as part of bipolar disorders.
PharmacodynamicsChlorprothixene is a typical antipsychotic drug of the thioxanthine class. It has a low antipsychotic potency (half to 2/3 of chlorpromazine). An intrinsic antidepressant effect of chlorprothixene has been discussed, but not proven yet. Likewise, it is unclear, if chlorprothixene has genuine analgesic effects. An antiemetic effect, as with most antipsychotics, exists. 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 strong sedative activity with a high incidence of anticholinergic side-effects. Chlorprothixene is structurally related to chlorpromazine, with which it shares in principal all side effects. Allergic side-effects and liver damage seem to appear with an appreciable lower frequency.
Mechanism of actionChlorprothixene 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.
AbsorptionIncomplete bioavailability.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic

Route of eliminationNot Available
Half life8 to 12 hours
ClearanceNot Available
ToxicitySymptoms 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).
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9899
Blood Brain Barrier+0.95
Caco-2 permeable+0.7404
P-glycoprotein substrateSubstrate0.8042
P-glycoprotein inhibitor IInhibitor0.8407
P-glycoprotein inhibitor IIInhibitor0.8884
Renal organic cation transporterInhibitor0.72
CYP450 2C9 substrateNon-substrate0.7199
CYP450 2D6 substrateSubstrate0.6845
CYP450 3A4 substrateSubstrate0.7096
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.768
Ames testNon AMES toxic0.7084
CarcinogenicityNon-carcinogens0.8714
BiodegradationNot ready biodegradable0.9838
Rat acute toxicity3.1665 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8117
hERG inhibition (predictor II)Inhibitor0.7373
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point153-154Sprague, 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 solubility0.295 mg/LNot Available
logP5.18HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.000366 mg/mLALOGPS
logP5.42ALOGPS
logP5.07ChemAxon
logS-5.9ALOGPS
pKa (Strongest Basic)9.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity104.66 m3·mol-1ChemAxon
Polarizability35.85 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (8.22 KB)
SpectraNot Available
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 ReferencesNot Available
External Links
ATC CodesN05AF03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (63.3 KB)
Interactions
Drug Interactions
Drug
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Chlorprothixene.
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Chlorprothixene.
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Chlorprothixene.
AmphetamineChlorprothixene may decrease the stimulatory activities of Amphetamine.
BenzphetamineChlorprothixene may decrease the stimulatory activities of Benzphetamine.
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Chlorprothixene.
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Chlorprothixene.
CitalopramThe risk or severity of adverse effects can be increased when Citalopram is combined with Chlorprothixene.
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Chlorprothixene.
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Chlorprothixene.
DesipramineThe risk or severity of adverse effects can be increased when Desipramine is combined with Chlorprothixene.
DesvenlafaxineThe risk or severity of adverse effects can be increased when Desvenlafaxine is combined with Chlorprothixene.
DextroamphetamineChlorprothixene may decrease the stimulatory activities of Dextroamphetamine.
DextromethorphanThe risk or severity of adverse effects can be increased when Dextromethorphan is combined with Chlorprothixene.
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Chlorprothixene.
DonepezilDonepezil may increase the central neurotoxic activities of Chlorprothixene.
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Chlorprothixene.
DuloxetineThe risk or severity of adverse effects can be increased when Duloxetine is combined with Chlorprothixene.
EletriptanThe risk or severity of adverse effects can be increased when Eletriptan is combined with Chlorprothixene.
Ergoloid mesylateThe risk or severity of adverse effects can be increased when Ergoloid mesylate is combined with Chlorprothixene.
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Chlorprothixene.
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Chlorprothixene.
EscitalopramThe risk or severity of adverse effects can be increased when Escitalopram is combined with Chlorprothixene.
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Chlorprothixene.
FluoxetineThe risk or severity of adverse effects can be increased when Fluoxetine is combined with Chlorprothixene.
FluvoxamineThe risk or severity of adverse effects can be increased when Fluvoxamine is combined with Chlorprothixene.
FrovatriptanThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Chlorprothixene.
GalantamineGalantamine may increase the central neurotoxic activities of Chlorprothixene.
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Chlorprothixene.
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Chlorprothixene.
LevomilnacipranThe risk or severity of adverse effects can be increased when Levomilnacipran is combined with Chlorprothixene.
LinezolidThe risk or severity of adverse effects can be increased when Linezolid is combined with Chlorprothixene.
LisdexamfetamineChlorprothixene may decrease the stimulatory activities of Lisdexamfetamine.
LithiumLithium may increase the neurotoxic activities of Chlorprothixene.
LorcaserinThe risk or severity of adverse effects can be increased when Lorcaserin is combined with Chlorprothixene.
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Chlorprothixene.
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Chlorprothixene.
MethamphetamineChlorprothixene may decrease the stimulatory activities of Methamphetamine.
MethylphenidateThe risk or severity of adverse effects can be increased when Chlorprothixene is combined with Methylphenidate.
MetoclopramideThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Chlorprothixene.
MetyrosineThe risk or severity of adverse effects can be increased when Metyrosine is combined with Chlorprothixene.
MilnacipranThe risk or severity of adverse effects can be increased when Milnacipran is combined with Chlorprothixene.
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Chlorprothixene.
NaratriptanThe risk or severity of adverse effects can be increased when Naratriptan is combined with Chlorprothixene.
NefazodoneThe risk or severity of adverse effects can be increased when Nefazodone is combined with Chlorprothixene.
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Chlorprothixene.
ParoxetineThe risk or severity of adverse effects can be increased when Paroxetine is combined with Chlorprothixene.
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Chlorprothixene.
PhendimetrazineChlorprothixene may decrease the stimulatory activities of Phendimetrazine.
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Chlorprothixene.
PhentermineChlorprothixene may decrease the stimulatory activities of Phentermine.
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Chlorprothixene.
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Chlorprothixene.
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Chlorprothixene.
QuinagolideThe therapeutic efficacy of Quinagolide can be decreased when used in combination with Chlorprothixene.
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Chlorprothixene.
RivastigmineRivastigmine may increase the central neurotoxic activities of Chlorprothixene.
RizatriptanThe risk or severity of adverse effects can be increased when Rizatriptan is combined with Chlorprothixene.
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Chlorprothixene.
SertralineThe risk or severity of adverse effects can be increased when Sertraline is combined with Chlorprothixene.
SumatriptanThe risk or severity of adverse effects can be increased when Sumatriptan is combined with Chlorprothixene.
Tedizolid PhosphateThe risk or severity of adverse effects can be increased when Tedizolid Phosphate is combined with Chlorprothixene.
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Chlorprothixene.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Chlorprothixene.
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Chlorprothixene.
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Chlorprothixene.
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Chlorprothixene.
VenlafaxineThe risk or severity of adverse effects can be increased when Venlafaxine is combined with Chlorprothixene.
VilazodoneThe risk or severity of adverse effects can be increased when Vilazodone is combined with Chlorprothixene.
VortioxetineThe risk or severity of adverse effects can be increased when Vortioxetine is combined with Chlorprothixene.
ZolmitriptanThe risk or severity of adverse effects can be increased when Zolmitriptan is combined with Chlorprothixene.
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.

Targets

1. D(2) dopamine receptor

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
D(2) dopamine receptor P14416 Details

References:

  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Epub 2008 Sep 7. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. D(1A) dopamine receptor

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
D(1A) dopamine receptor P21728 Details

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
  3. 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. Pubmed

3. D(3) dopamine receptor

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
D(3) dopamine receptor P35462 Details

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
  3. 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. Pubmed

4. 5-hydroxytryptamine receptor 2A

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2A P28223 Details

References:

  1. 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. Pubmed
  2. 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. Pubmed

5. 5-hydroxytryptamine receptor 2B

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2B P41595 Details

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. 5-hydroxytryptamine receptor 2C

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2C P28335 Details

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. Histamine H1 receptor

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

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

8. Muscarinic acetylcholine receptor M1

Kind: Protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M1 P11229 Details

References:

  1. 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. Pubmed

9. Muscarinic acetylcholine receptor M2

Kind: Protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M2 P08172 Details

References:

  1. 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. Pubmed

10. Muscarinic acetylcholine receptor M3

Kind: Protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M3 P20309 Details

References:

  1. 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. Pubmed

11. Muscarinic acetylcholine receptor M4

Kind: Protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M4 P08173 Details

References:

  1. 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. Pubmed

12. Muscarinic acetylcholine receptor M5

Kind: Protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M5 P08912 Details

References:

  1. 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. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. 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. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on January 15, 2016 17:38