QuickView for Chlorpromazine (compound)

Summary
General Info

PubChem

PubChem Compound 11380

Name:	Chlorpromazine
PubChem Compound ID:	11380
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.
Molecular formula:	C₁₁H₂₀ClN₅
Molecular weight:	257.763 g/mol
Synonyms:	1,3,5-Triazine-2,4-diamine, 6-chloro-N,N,N',N'-tetraethyl-; G 25,804; Geigy herbicide 444E; s-Triazine, 2-chloro-4,6-bis (diethylamino)-; 4-26-00-01208 (Beilstein Handbook Reference); 6-Chloro-N,N,N',N'-tetraethyl-1,3,5-triazine-2,4-diamine; CBDivE_012578; Geigy 444E; 2-Chloro-4,6-bis(diethylamino)-1,3,5-triazine; G 444E. show more » 1,3,5-Triazine-2,4-diamine, 6-chloro-N,N,N',N'-tetraethyl-; G 25,804; Geigy herbicide 444E; s-Triazine, 2-chloro-4,6-bis (diethylamino)-; 4-26-00-01208 (Beilstein Handbook Reference); 6-Chloro-N,N,N',N'-tetraethyl-1,3,5-triazine-2,4-diamine; CBDivE_012578; Geigy 444E; 2-Chloro-4,6-bis(diethylamino)-1,3,5-triazine; G 444E; 2,4-Bis(diethylamino)-6-chloro-s-triazine; NSC56840; NSC 56840; Chloroazine; NCIOpen2_002382; BRN 0020617; HSDB 1534; 1,3, 5-Triazine-2,4-diamine, 6-chloro-N,N,N',N'-tetraethyl-; NCIOpen2_002443; Phenazon; 6-Chloro-N,N,N', N'-tetraethyl-1,3,5-triazine-2,4-diamine; EPA Pesticide Chemical Code 080806; EINECS 209-459-3; Chlorazin; 2-Chloro-4,6-bis(diethylamino)-s-triazine; NSC 56355; NSC56355; s-Triazine, 2-chloro-4,6-bis(diethylamino)-; Caswell No. 172; CHLORAZINE; 580-48-3; 1,3,5-Triazine-2,4-diamine, 6-chloro-N,N,N',N'-tetraethyl- (9CI) show less «

DrugBank

Identification

Name:	Chlorpromazine
Name (isomeric):	DB00477
Drug Type:	small molecule
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.
Synonyms:	Chlorpromazine hydrochloride
Brand:	Largactil Liquid, Thorazine Spansule, Intensol, Largactil Oral Drops, Chlorpromanyl (discontinued), Novo-Chlorpromazine
Category:	Phenothiazines, Antiemetics, Dopamine Antagonists, Antipsychotic Agents, Antipsychotics
CAS number:	50-53-3

Pharmacology

Indication:	For the treatment of schizophrenia, control nausea and vomiting, For relief of restlessness and apprehension before surgery, adjunct in the treatment of tetanus, control the manifestations of the manic type of manic-depressive illness.
Pharmacology:	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 anticholiner... show more » 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. show less «
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 atten... show more » 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). show less «
Absorption:	Readily absorbed from the GI tract. Bioavailability varies due to first-pass metabolism by the liver.
Protein binding:	> 90% to plasma proteins, primarily albumin
Biotransformation:	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
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

Interactions

Food interaction:

Avoid alcohol.

Take with food to reduce irritation.

Drug interaction:

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Levofloxacin	Increased risk of cardiotoxicity and arrhythmias
Triprolidine	The antihistamine, Triprolidine, may increase the arrhythmogenic effect of the phenothiazine, Chlorpromazine. Monitor for symptoms of ventricular arrhythmias. Additive anticholinergic and CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Metrizamide	Increased risk of convulsions
Amphetamine	Decreased anorexic effect, may increase psychotic symptoms

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Levofloxacin	Increased risk of cardiotoxicity and arrhythmias
Triprolidine	The antihistamine, Triprolidine, may increase the arrhythmogenic effect of the phenothiazine, Chlorpromazine. Monitor for symptoms of ventricular arrhythmias. Additive anticholinergic and CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Metrizamide	Increased risk of convulsions
Amphetamine	Decreased anorexic effect, may increase psychotic symptoms
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias
Tetrabenazine	May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Trimethobenzamide	Trimethobenzamide and Chlorpromazine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Phenylpropanolamine	Decreased anorexic effect, may increase psychotic symptoms
Bromocriptine	The phenothiazine decreases the effect of bromocriptine
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tolterodine	Chlorpromazine may decrease the metabolism and clearance of Tolterodine. Monitor for adverse/toxic effects of Tolterodine.
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
Mazindol	Decreased anorexic effect, may increase psychotic symptoms
Propranolol	Increased effect of both drugs
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Chlorpromazine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if chlorpromazine is initiated, discontinued or dose changed.
Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Methamphetamine	Decreased anorexic effect, may increases psychotic symptoms
Galantamine	Possible antagonism of action
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Chlorpromazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Tamsulosin	Chlorpromazine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Chlorpromazine is initiated, discontinued, or dose changed.
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Gatifloxacin	Increased risk of cardiotoxicity and arrhythmias
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Phenmetrazine	Decreased anorexic effect, may increase psychotic symptoms
Rivastigmine	Possible antagonism of action
Phendimetrazine	Decreased anorexic effect, may increases psychotic symptoms
Diethylpropion	Decreased anorexic effect, may increase psychotic symptoms
Guanethidine	Chlorpromazine may decrease the effect of guanethidine.
Phentermine	Decreased anorexic effect, may increase psychotic symptoms
Meperidine	Increased sedation and hypotension
Donepezil	Possible antagonism of action
Tamoxifen	Chlorpromazine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
Mesoridazine	Increased risk of cardiotoxicity and arrhythmias
Benzphetamine	Antipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Terbinafine	Terbinafine may reduce the metabolism and clearance of Chlorpromazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Chlorpromazine if Terbinafine is initiated, discontinued or dose changed.
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Trimipramine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Chlorpromazine, a strong CYP2D6 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Caution should be used during concomitant therapy.
Tramadol	Chlorpromazine may decrease the effect of Tramadol by decreasing active metabolite production.
Venlafaxine	Chlorpromazine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Chlorpromazine is initiated, discontinued, or dose changed.
Fenfluramine	Decreased anorexic effect, may increase psychotic symptoms
Pindolol	Increased effect of both drugs
Trospium	Trospium and Chlorpromazine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Dexfenfluramine	Decreased anorexic effect, may increase psychotic symptoms.
Dextroamphetamine	Decreased anorexic effect, may increases psychotic symptoms