Desmethyldesipramine

A metabolite of the tricyclic antidepressant desipramine

Desmethyldesipramine is a pharmacologically active metabolite of the tricyclic antidepressant desipramine. It is formed in the body through the process of N-demethylation, primarily in the liver. Desmethyldesipramine retains some of the pharmacological properties of its parent compound, contributing to the overall therapeutic effects and side effects observed in patients undergoing treatment with desipramine.

Pharmacology

Desmethyldesipramine acts primarily as a norepinephrine reuptake inhibitor, similar to desipramine. This action increases the concentration of norepinephrine in the synaptic cleft, enhancing noradrenergic neurotransmission. This mechanism is believed to contribute to its antidepressant effects.

Metabolism

Desipramine is metabolized in the liver by the cytochrome P450 enzyme system, particularly by CYP2D6. The N-demethylation of desipramine to form desmethyldesipramine is a major metabolic pathway. The activity of CYP2D6 can vary significantly between individuals due to genetic polymorphisms, which can affect the plasma levels of both desipramine and desmethyldesipramine.

Pharmacokinetics

The pharmacokinetics of desmethyldesipramine are influenced by its lipophilicity and protein binding. It is distributed widely throughout the body and crosses the blood-brain barrier. The elimination half-life of desmethyldesipramine is similar to that of desipramine, contributing to the drug's overall duration of action.

Clinical Significance

The presence of desmethyldesipramine in the plasma can be significant in the context of therapeutic drug monitoring. Measuring the levels of both desipramine and its metabolite can provide insights into the patient's metabolic status and help in adjusting dosages to achieve optimal therapeutic effects while minimizing side effects.

Side Effects

Desmethyldesipramine, like desipramine, can contribute to side effects such as dry mouth, constipation, urinary retention, and cardiovascular effects like tachycardia and orthostatic hypotension. These side effects are typical of tricyclic antidepressants and are related to their anticholinergic and adrenergic properties.

Also see

• Desipramine
• Tricyclic antidepressant
• Norepinephrine reuptake inhibitor
• Cytochrome P450
• Therapeutic drug monitoring