Clomipramine Hydrochloride

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Cat Number

API17321776

CAS Number

17321-77-6

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CAS Number

17321-77-6

EINECS

241-344-3

Storage

2-8℃

Synonyms

Clomipramine HCl;3-chloro-5-(3-(dimethylamino)propyl)-10,11-dihydro-5h-dibenz(b,f)azepinemono;3-chloroimipraminehydrochloride

Molecular Formula

C19H24Cl2N2

Molecular Weight

351.3

Smiles

CN(C)CCCN1C2=CC=CC=C2CCC3=C1C=C(C=C3)Cl.Cl

Appearance

White to off-white solid

Melting Point

189-190℃

General Description

Clomipramine Hydrochloride is a tricyclic antidepressant of the dibenzazepine class. It is distinguished from other TCAs by its particularly potent inhibition of serotonin reuptake relative to norepinephrine reuptake.

Mechanism of Action

Clomipramine inhibits presynaptic reuptake of serotonin with high affinity, increasing synaptic serotonin concentrations. It also antagonizes histamine H1, muscarinic, and alpha-1 adrenergic receptors, contributing to its side-effect profile.

Application

Used in the treatment of obsessive-compulsive disorder and depression. Clomipramine Hydrochloride is indicated for OCD, major depressive disorder, panic disorder, and cataplexy associated with narcolepsy.

Clomipramine hydrochloride was identified as an irreversible inhibitor of the HECT-type ubiquitin ligase ITCH through high-throughput screening of a chemical library. Biochemical assays demonstrated that clomipramine blocked ITCH auto-ubiquitylation activity in an irreversible manner, as ubiquitylation activity remained absent after dialysis of clomipramine-pretreated ITCH samples. Clomipramine also inhibited other HECT E3 ligases but not RING E3 ligases, suggesting a HECT-domain-specific mechanism.
Structural analogs of clomipramine revealed that the chloride group on the aromatic moiety and the length of the side chain are critical for ITCH inhibitory activity. Docking studies showed that clomipramine may bind between the N- and C-lobes of the ITCH HECT domain or interact directly with the catalytic cysteine residue. The compound also blocked autophagic flux and synergized with chemotherapeutics to inhibit cancer cell growth.

Fig. 1 Schematic representation of the layout of the ELISA assay used for the HTS. (Amelio I.; et al. 2014)

References

Amelio I, et al. High throughput screening for inhibitors of the HECT ubiquitin E3 ligase ITCH identifies antidepressant drugs as regulators of autophagy. Cell Death & Disease, 2014, 5(5): e1203-e1203.

What makes Clomipramine particularly effective for OCD?

Clomipramine has the strongest serotonin reuptake inhibition among TCAs, and its active metabolite desmethylclomipramine adds noradrenergic activity, providing dual benefit for OCD.