Description

Clomipramine HCl (hydrochloride), also known by its brand name Anafranil, is a tricyclic antidepressant (TCA). It is a dibenzazepine derivative that comes in capsule form for oral administration. Clomipramine is an antidepressant and antiobsessional drug.

Indications

Clomipramine is a medication primarily used to treat obsessive-compulsive disorder (OCD) in adults and children 10 years of age and older. It was the first drug approved by the FDA specifically for this purpose.

It is also used off-label for a number of other conditions, including:

• Major depressive disorder
• Panic disorder
• Chronic pain syndromes
• Narcolepsy-associated cataplexy
• Trichotillomania (hair-pulling disorder)
• Body dysmorphic disorder
• Premature ejaculation

Mechanism of Action

The therapeutic effect of clomipramine is not fully understood, but it is believed to work by influencing neurotransmission in the brain. Its primary mechanism is the potent inhibition of the reuptake of two key neurotransmitters: serotonin (5-HT) and norepinephrine (NE).

• Serotonin and Norepinephrine Reuptake Inhibition: Clomipramine blocks the reabsorption of serotonin and norepinephrine back into the presynaptic nerve terminals. This action increases the concentration of these neurotransmitters in the synaptic cleft (the space between neurons), enhancing their availability to bind with postsynaptic receptors. This increased neurotransmission is thought to be responsible for its antidepressant and antiobsessional effects.
• Role of Active Metabolites: Clomipramine is extensively metabolized in the liver to form an active metabolite called desmethylclomipramine. While clomipramine itself has a stronger affinity for the serotonin transporter, its metabolite, desmethylclomipramine, is a more potent inhibitor of norepinephrine reuptake. This dual action on both serotonin and norepinephrine pathways contributes to its overall therapeutic effect.
• Other Receptor Interactions: Clomipramine also interacts with and blocks several other receptors, including histamine H1 receptors, muscarinic acetylcholine receptors, and alpha-adrenergic receptors. These interactions are not related to its primary therapeutic effects but are responsible for many of its common side effects, such as sedation, dry mouth, constipation, and dizziness.