Rapid down-regulation of serotonin2 receptor binding during combined administration of tricyclic antidepressant drugs and alpha 2 antagonists.

Recent studies have shown that chronic, but not acute, treatment with several different antidepressant drugs decreases the density of serotonin2 (5HT2) receptors in the cerebral cortex (Peroutka and Snyder, 1980a). It was found that combined administration of antidepressant drugs with alpha 2 antagonists could accelerate this down-regulation of 5HT2 receptors induced by antidepressants. Amitriptyline (10 mg/kg, twice daily) in combination with yohimbine (5 mg/kg, twice daily) decreased 5HT2 receptor binding after 4 days of treatment, whereas amitriptyline alone required 10 days to decrease the density of 5HT2 receptors. Other antidepressant--alpha-antagonist combinations which rapidly decreased the density of 5HT2 receptors were desipramine-phenoxybenzamine, amitriptyline-phenoxybenzamine, iprindole-phenoxybenzamine, mianserin-phenoxybenzamine and desipramine-dihydroergotamine. Treatment with desipramine in combination with prazosin, an alpha 1 antagonist, did not accelerate the down-regulation of 5HT2 receptors induced by antidepressants. These results suggest that blockade of central alpha 2 receptors can accelerate the down-regulation of 5HT2 receptors by antidepressants. A combination of antidepressant and alpha antagonist treatment could represent a new, rapid onset antidepressant drug therapy.