Dosulepin: Mechanism of Action and Pharmacology

Article Plan⁚ Dosulepin⁚ Mechanism of Action and Pharmacology

General Information

Dosulepin, also known as dothiepin, is a tricyclic antidepressant with anxiolytic properties that has been used in several European and South Asian countries, as well as in Australia, South Africa, and New Zealand.​ Despite once being a commonly prescribed antidepressant, its usage has declined due to its relatively high toxicity in overdose without significant therapeutic advantages over other tricyclic antidepressants.​

Dosulepin inhibits the reuptake of monoamine neurotransmitters in the central nervous system, leading to an increased concentration of neurotransmitters in the synaptic cleft and exerting an antidepressant effect.​ It particularly affects the uptake of noradrenaline and serotonin, contributing to its pharmacological actions.​

Mechanism of Action

Dosulepin, also known as dothiepin, exerts its pharmacological effects by inhibiting the reuptake of noradrenaline, dopamine, and serotonin in the central nervous system.​ This action leads to an increased concentration of these neurotransmitters in the synaptic cleft, contributing to its antidepressant effects.​ Additionally, dosulepin possesses anticholinergic properties, further influencing its mechanism of action.​ The inhibition of neurotransmitter reuptake is a key aspect of dosulepin’s pharmacological activity, playing a crucial role in its therapeutic effects in the treatment of depression.​

Pharmacology

Dosulepin, a tricyclic antidepressant with anxiolytic properties, inhibits the reuptake of monoamine neurotransmitters, particularly noradrenaline and serotonin, in the central nervous system.​ This mechanism of action leads to increased neurotransmitter levels in the synaptic cleft, contributing to its therapeutic antidepressant effects.​ Dosulepin’s pharmacological activity involves its interaction with biogenic amines, resulting in alterations that play a crucial role in its antidepressant properties.​

Clinical Considerations

Clinical features of dosulepin overdose reflect the pharmacology of tricyclic antidepressants (TCAs).​ Antimuscarinic effects such as warm, dry skin, blurred vision, and urinary retention may occur.​ Additionally, effects on consciousness, respiration, and cardiovascular system can manifest, including hypotension, cardiac conduction abnormalities, and cardiac arrhythmias.​ Supportive treatment is often necessary, including activated charcoal to prevent further absorption, seizure management, and correction of hypoxia and acidosis.​ Hallucinations and delirium may occur during recovery, and cardiac complications should be monitored and managed accordingly.​

Research and Studies

One study explored the half-life and metabolism of Dosulepin (Dothiepin), revealing that it is metabolized in the liver into three pharmacologically active metabolites⁚ nordosulepine, dosulepine sulfoxide, and nordosulepine sulfoxide.​ The investigation provided insights into the pharmacokinetics and metabolites of Dosulepin, shedding light on its pharmacological profile and potential effects.