| Candidate ID: | R0462 |
| Source ID: | DB01242 |
| Source Type: | approved; investigational; vet_approved |
| Compound Type: |
small molecule
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| Compound Name: |
Clomipramine
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| Synonyms: |
3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethyl-1-propanamine; 3-(3-chloro-5H-dibenzo[b,F]azepin-5-yl)-N,N-dimethylpropan-1-amine; 3-Chloroimipramine; Chlorimipramine; Clomipramine; Monochlorimipramine
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| Molecular Formula: |
C19H23ClN2
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| SMILES: |
CN(C)CCCN1C2=CC=CC=C2CCC2=C1C=C(Cl)C=C2
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| Structure: |
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| DrugBank Description: |
Clomipramine, the 3-chloro analog of imipramine, is a dibenzazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, clomipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, clomipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as clomipramine, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H<sub>1</sub> receptors, α<sub>1</sub>-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Clomipramine 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 panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy, autistic disorder, trichotillomania, onchophagia, stuttering, premature ejaculation, and premenstrual syndrome. Clomipramine is rapidly absorbed from the gastrointestinal tract and demethylated in the liver to its primary active metabolite, desmethylclomipramine.
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| CAS Number: |
303-49-1
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| Molecular Weight: |
314.852
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| DrugBank 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.
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| DrugBank 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 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: α<sub>1</sub> and β<sub>1</sub> receptors are sensitized, α<sub>2</sub> 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.
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| DrugBank MoA: |
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. α<sub>1</sub>-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.
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| Targets: |
Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 2B antagonist; 5-hydroxytryptamine receptor 2C antagonist; Sodium-dependent noradrenaline transporter inhibitor; Glutathione S-transferase P inhibitor
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| Inclusion Criteria: |
Indication associated
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