QuickView for chlorimipramine (compound)

Summary
General Info

PubChem

PubChem Compound 2801

Name:	Clomipramine
PubChem Compound ID:	2801
Description:	A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.
Molecular formula:	C₁₉H₂₃ClN₂
Molecular weight:	314.852 g/mol
Synonyms:	KBio2_006060; 5H-Dibenz(b,f)azepine-5-propanamine, 3-chloro-10,11-dihydro-N,N-dimethyl-; Tocris-0457; G 34586; Spectrum2_001729; KBio1_000797; Clomipramine; 5H-Dibenz(b,f)azepine, 3-chloro-5-(3-(dimethylamino)propyl)-10,11-dihydro- (8CI); Lopac-C-7291; SPBio_001778. show more » KBio2_006060; 5H-Dibenz(b,f)azepine-5-propanamine, 3-chloro-10,11-dihydro-N,N-dimethyl-; Tocris-0457; G 34586; Spectrum2_001729; KBio1_000797; Clomipramine; 5H-Dibenz(b,f)azepine, 3-chloro-5-(3-(dimethylamino)propyl)-10,11-dihydro- (8CI); Lopac-C-7291; SPBio_001778; 5H-Dibenz[b, f]azepine-5-propanamine, 3-chloro-10,11-dihydro-N,N-dimethyl-; KBioGR_000759; Chlorimipramine; 5H-Dibenz[b,f]azepine-5-propanamine, 3-chloro-10,11-dihydro-N,N-dimethyl-; AIDS-059769; 83162-38-3; 17321-77-6; 5H-Dibenz(b,f)azepine, 10,11-dihydro-3-chloro-5-(3-(dimethylamino)propyl)-; KBio2_000924; NSC169865; Spectrum_000444; Monochlorimipramine; KBioSS_000924; NCGC00015264-02; NCGC00015264-01; 303-49-1; 5H-Dibenz[b, f]azepine, 3-chloro-5-[3- (dimethylamino)propyl]-10,11-dihydro-; 5-20-08-00103 (Beilstein Handbook Reference); BRN 1323477; Clomipramina [INN-Spanish]; Hydiphen; AIDS059769; KBio3_002514; 5H-Dibenz(b,f)azepine, 3-chloro-5-(3-(dimethylamino)propyl)-10,11-dihydro-; Anafranil (free base); Prestwick1_000269; Spectrum3_001707; 3-Chloro-5-(3-(dimethylamino)propyl)-10,11-dihydro-5H-dibenz(b,f)azepine; Prestwick0_000269; 3-Chloro-5-[3-(dimethylamino)propyl]-10, 11-dihydro-5H-dibenz[b,f]azepine; 3-Chloroimipramine; CAS-17321-77-6; DivK1c_000797; 5H-Dibenz[b,f]azepine, 10, 11-dihydro-3-chloro-5-[3-(dimethylamino)propyl]-; C06918; Clomipraminum [INN-Latin]; G-34586; Spectrum4_000350; 3-chloro-10,11-dihydro-N,N-dimethyl-5H-Dibenz(b,f)azepine-5-propanamine; SPBio_002337; NSC 169865; 10,11-dihydro-3-chloro-5-(3-(dimethylamino)propyl)-5H-dibenz(b,f)azepine; KBio2_003492; EINECS 206-144-2; NINDS_000797; Anafranil base; NCGC00024355-02 show less «

DrugBank

Identification

Name:	Clomipramine
Name (isomeric):	DB01242
Drug Type:	small molecule
Description:	A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.
Synonyms:	3-Chloroimipramine; Clomipramine HCL; Chlorimipramine; Monochlorimipramine; Clomipraminum [INN-Latin]; Clomipramina [INN-Spanish]
Brand:	Hydiphen, Anafranil
Category:	Serotonin Uptake Inhibitors, Antidepressive Agents, Tricyclic
CAS number:	303-49-1

Pharmacology

Indication:	May be used to treat obsessive-compulsive disorder and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette’s disorder). Unlabeled indications include: depression, panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy (limited evidence), autistic disorder (limited evidence), trichotillomania (limited evidence), onchophagia (limited evidence), stuttering (limited evidence), premature ejaculation, and premenstrual syndrome.
Pharmacology:	Clomipramine, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought... show more » Clomipramine, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: α₁ and β₁ receptors are sensitized, α₂ receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. show less «
Mechanism of Action:	Clomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of noradrenaline reuptake. α₁-receptor blockage and β-down-regulation have been noted and most likely play a role in the short term effects of clomipramin... show more » Clomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of noradrenaline reuptake. α₁-receptor blockage and β-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type. show less «
Absorption:	Well absorbed from the GI tract following oral administration. Bioavailability is approximately 50% orally due to extensive first-pass metabolism. Bioavailability is not affected by food. Peak plasma concentrations occur 2-6 hours following oral administration of a single 50 mg dose. Large interindividual variations in plasma concentrations occur, partly due to genetic differences in clomipramine metabolism. On average, steady state plasma concentrations are achieved in 1-2 weeks following multiple dose oral administration. Smoking appears to lower the steady-state plasma concentration of clomipramine, but not its active metabolite desmethylclomipramine.
Protein binding:	Clomipramine is approximately 97-98% bound to plasma proteins, principally to albumin and possibly to α₁-acid glycoprotein. Desmethylclomipramine is 97-99% bound to plasma proteins.
Biotransformation:	Extensively metabolized in the liver. The main active metabolite is desmethylclomipramine, which is formed by N-demethylation of clomipramine via CYP2C19, 3A4 and 1A2. Other metabolites and their glucuronide conjugates are also produced. Other metabolites of clomipramine include 8-hydroxyclomipramine formed via 8-hydroxylation, 2-hydroxyclomipramine formed via 2-hydroxylation, and clomipramine N-oxide formed by N-oxidation. Desmethylclomipramine is further metabolized to 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which are formed by 8-hydroxylation and N-demethylation, respectively. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine are pharmacologically active; however, their clinical contribution remains unknown.
Route of elimination:	Urine (51-60%) and feces via biliary elimination (24-32%)
Half Life:	Following oral administration of a single 150 mg dose of clomipramine, the average elimination half-life of clomipramine was 32 hours (range: 19-37 hours) and of desmethylclomipramine was 69 hours (range: 54-77 hours). Elimination half-life may vary substantially with different doses due to probably saturable kinetics (i.e. metabolism).
Toxicity:	Signs and symptoms vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient, and the time elapsed since drug ingestion. Critical manifestations of overdose include cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic toxicity. In U.S. clinical trials, 2 deaths occurred in 12 reported cases of acute overdosage with Anafranil either alone or in combination with other drugs. One death involved a patient suspected of ingesting a dose of 7000 mg. The second death involved a patient suspected of ingesting a dose of 5750 mg. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Avoid alcohol.

Take with food to reduce irritation.

Grapefruit and grapefruit juice should be avoided throughout treatment, grapefruit can modify serum levels of clomipramine and its metabolite desmethyl-clomipramine.

Drug interaction:

Terbinafine	Terbinafine may reduce the metabolism and clearance of Clomipramine. Consider alternate therapy or monitor for therapeutic/adverse effects of Clomipramine if Terbinafine is initiated, discontinued or dose changed.
Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Dihydroquinidine barbiturate	Dihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, clomipramine.
Tamoxifen	Clomipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias

Terbinafine	Terbinafine may reduce the metabolism and clearance of Clomipramine. Consider alternate therapy or monitor for therapeutic/adverse effects of Clomipramine if Terbinafine is initiated, discontinued or dose changed.
Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Dihydroquinidine barbiturate	Dihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, clomipramine.
Tamoxifen	Clomipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias
Ticlopidine	Ticlopidine may decrease the metabolism and clearance of Clomipramine. Consider alternate therapy or monitor for adverse/toxic effects of Clomipramine if Ticlopidine is initiated, discontinued or dose changed.
Tranylcypromine	Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
Fenoterol	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of fenoterol.
Isoproterenol	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of isoproterenol.
Cimetidine	Cimetidine may increase the effect of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if cimetidine is initiated, discontinued or dose changed.
Tramadol	Tramadol increases the risk of serotonin syndrome and seizures. Clomipramine may decrease the effect of Tramadol by decreasing active metabolite production.
Procaterol	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of procaterol.
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Epinephrine	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of epinephrine.
Rifabutin	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, clomipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if rifabutin is initiated, discontinued or dose changed.
Quinidine	Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
Phenelzine	Possibility of severe adverse effects
Atazanavir	Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if atazanavir is initiated, discontinued or dose changed.
Dobutamine	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of dobutamine.
Moclobemide	Possible severe adverse reaction with this combination
Phenylephrine	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of phenylephrine.
Galantamine	Possible antagonism of action
Pseudoephedrine	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of pseudoephedrine.
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Zolmitriptan	Use of two serotonin modulators, such as zolmitriptan and clomipramine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Methoxamine	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of methoxamine.
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.
Isocarboxazid	Possibility of severe adverse effects
Rivastigmine	Possible antagonism of action
Trimipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Dopamine	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of dopamine.
Metaraminol	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of metaraminol.
Rifampin	The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, clomipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if rifampin is initiated, discontinued or dose changed.
Ephedrine	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of ephedrine.
Voriconazole	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Pirbuterol	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of pirbuterol.
Ritonavir	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if ritonavir if initiated, discontinued or dose changed.
Triprolidine	Triprolidine and Clomipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Sibutramine	Increased risk of CNS adverse effects
Norepinephrine	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of norepinephrine.
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Donepezil	Possible antagonism of action
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).
Trimethobenzamide	Trimethobenzamide and Clomipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Fluvoxamine	The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of clomipramine if fluvoxamine is initiated, discontinued or dose changed.
Altretamine	Risk of severe hypotension
Tamsulosin	Clomipramine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clomipramine is initiated, discontinued, or dose changed.
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Clomipramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Mephentermine	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of mephentermine.
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Butalbital	Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as clomipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Salbutamol	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of salbutamol.
Ephedra	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of ephedra.
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).
Trospium	Trospium and Clomipramine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Butabarbital	Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like clomipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Orciprenaline	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of orciprenaline.
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Clonidine	The tricyclic antidepressant, clomipramine, may decrease the effect of clonidine.
Quinidine barbiturate	Quinidine barbiturate increases the effect of tricyclic antidepressant, clomipramine.
Phenylpropanolamine	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of phenylpropanolamine.
Terbutaline	The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of terbutaline.
Guanethidine	The tricyclic antidepressant, clomipramine, decreases the effect of guanethidine.
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Rasagiline	Possibility of severe adverse effects
Fluoxetine	The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of clomipramine if fluoxetine is initiated, discontinued or dose changed.
Thiabendazole	The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Clomipramine by decreasing Clomipramine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Clomipramine if Thiabendazole is initiated, discontinued or dose changed.

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Targets

Sodium-dependent serotonin transporter

5-hydroxytryptamine 2A receptor

5-hydroxytryptamine 2B receptor

5-hydroxytryptamine 2C receptor

Sodium-dependent noradrenaline transporter

Glutathione S-transferase P

Enzymes

Transporters

Multidrug resistance protein 1