Dosulepin is indicated in the treatment of symptoms of depressive illness, especially where an anti-anxiety effect is required. Dosulepin displays affinity towards α2-adrenoceptors and to a lesser extent, α1-adrenoceptors. Inhibition of presynaptic α2-adrenoceptors by dosulepin facilitates noradrenaline release and further potentiates the antidepressant effects. It also downregulates central β-adrenoceptors by causing a decline in the number of receptors and reduces noradrenaline-induced cyclic AMP formation. Dosulepin binds to 5HT1A and 5HT2A receptors in the cerebral cortex and hippocampus as an antagonist. 5HT1A receptors are autoreceptors that inhibit 5HT release and 5HT2A receptors are Gi/Go-coupled receptors that reduces dopamine release upon activation. Antagonism at 5HT2A receptors may also improve sleep patterns. Dosulepin also binds to muscarinic acetylcholine receptors and causes antimuscarinic side effects such as dry mouth. By acting as an antagonist at histamine type 1 (H1) receptors, dosulepin mediates a sedative effect.

Dosulepin Serotonin antagonist pathway References