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药品详细

Chlorpromazine(氯丙嗪)

化学结构式图
中文名
氯丙嗪
英文名
Chlorpromazine
分子式
C17H19ClN2S
化学名
[3-(2-chloro-10H-phenothiazin-10-yl)propyl]dimethylamine
分子量
Average: 318.864
Monoisotopic: 318.095747015
CAS号
50-53-3
ATC分类
N05A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

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. [PubChem]

生产厂家
  • Abbott laboratories pharmaceutical products div
  • Abraxis pharmaceutical products
  • Actavis mid atlantic llc
  • Alpharma us pharmaceuticals division
  • Baxter healthcare corp anesthesia and critical care
  • Glaxosmithkline
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Kv pharmaceutical co
  • Lederle laboratories div american cyanamid co
  • Marsam pharmaceuticals llc
  • Parke davis div warner lambert co
  • Pharmaceutical assoc inc div beach products
  • Private formulations inc
  • Purepac pharmaceutical co
  • Roxane laboratories inc
  • Sandoz inc
  • Usl pharma inc
  • Vangard laboratories inc div midway medical co
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • Wockhardt eu operations (swiss) ag
  • Wyeth ayerst laboratories
封装厂家
参考
Synthesis Reference Not Available
General Reference
  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
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenothiazines
Substructures
  • Ethers
  • Phenothiazines
  • Aliphatic and Aryl Amines
  • Thiazines
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Anilines
适应症
药理
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.
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).
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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Chlorpromazine
hydroxychlorpromazine Details
Chlorpromazine
    		chlorpromazine-N-oxide Details
    Chlorpromazine
      		dedimethylchlorpromazine Details
      Chlorpromazine
        		demonomethylchlorpromazine Details
        Chlorpromazine
          		N-dedimethylchlorpromazine Details
          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
          理化性质
          Properties
          State liquid
          Experimental Properties
          Property Value Source
          melting point < 25 °C PhysProp
          boiling point 200-205 °C at 8.00E-01 mm Hg PhysProp
          water solubility 2.55 mg/L (at 24 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
          logP 5.41 AVDEEF,A (1995)
          logS -5.01 ADME Research, USCD
          Caco2 permeability -4.7 ADME Research, USCD
          pKa 9.3 (at 25 °C) HANSCH,C & LEO,AJ (1985)
          Predicted Properties
          Property Value Source
          water solubility 4.17e-03 g/l ALOGPS
          logP 5.18 ALOGPS
          logP 4.54 ChemAxon
          logS -4.9 ALOGPS
          pKa (strongest basic) 9.2 ChemAxon
          physiological charge 1 ChemAxon
          hydrogen acceptor count 2 ChemAxon
          hydrogen donor count 0 ChemAxon
          polar surface area 6.48 ChemAxon
          rotatable bond count 4 ChemAxon
          refractivity 93.76 ChemAxon
          polarizability 35.1 ChemAxon
          药物相互作用
          Drug Interaction
          Amphetamine Decreased anorexic effect, may increase psychotic symptoms
          Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
          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.
          Bromocriptine The phenothiazine decreases the effect of bromocriptine
          Cisapride Increased risk of cardiotoxicity and arrhythmias
          Dexfenfluramine Decreased anorexic effect, may increase psychotic symptoms.
          Dextroamphetamine Decreased anorexic effect, may increases psychotic symptoms
          Diethylpropion Decreased anorexic effect, may increase psychotic symptoms
          Dihydrocodeine Phenothiazines may enhance hypotensive effects of opioid analgesics. It is recommended to monitor patients for hypotension.
          Donepezil Possible antagonism of action
          Fenfluramine Decreased anorexic effect, may increase psychotic symptoms
          Galantamine Possible antagonism of action
          Gatifloxacin Increased risk of cardiotoxicity and arrhythmias
          Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
          Guanethidine Chlorpromazine may decrease the effect of guanethidine.
          Levofloxacin Increased risk of cardiotoxicity and arrhythmias
          Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
          Mazindol Decreased anorexic effect, may increase psychotic symptoms
          Meperidine Increased sedation and hypotension
          Mesoridazine Increased risk of cardiotoxicity and arrhythmias
          Methamphetamine Decreased anorexic effect, may increases psychotic symptoms
          Metrizamide Increased risk of convulsions
          Phendimetrazine Decreased anorexic effect, may increases psychotic symptoms
          Phenmetrazine Decreased anorexic effect, may increase psychotic symptoms
          Phentermine Decreased anorexic effect, may increase psychotic symptoms
          Phenylpropanolamine Decreased anorexic effect, may increase psychotic symptoms
          Pindolol Increased effect of both drugs
          Propranolol Increased effect of both drugs
          Rivastigmine Possible antagonism of action
          Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
          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.
          Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
          Tamoxifen Chlorpromazine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
          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.
          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
          Tetrabenazine May cause dopamine deficiency. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
          Thioridazine Increased risk of cardiotoxicity and arrhythmias
          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.
          Tolterodine Chlorpromazine may decrease the metabolism and clearance of Tolterodine. Monitor for adverse/toxic effects of Tolterodine.
          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.
          Tramadol Chlorpromazine may decrease the effect of Tramadol by decreasing active metabolite production.
          Trimethobenzamide Trimethobenzamide and Chlorpromazine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
          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.
          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.
          Trospium Trospium and Chlorpromazine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
          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.
          Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
          Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
          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.
          食物相互作用
          • Avoid alcohol.
          • Take with food to reduce irritation.

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