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QuickView for Clomipramine (compound)

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
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.
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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.
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
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.
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...
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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...
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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
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:
TerbinafineTerbinafine 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.
GrepafloxacinIncreased risk of cardiotoxicity and arrhythmias
Dihydroquinidine barbiturateDihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, clomipramine.
TamoxifenClomipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
SparfloxacinIncreased risk of cardiotoxicity and arrhythmias
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