Suppression of histamine-induced adrenocorticotropic hormone release by antihistamines and antidepressants

The antihistaminic activity of many antidepressant drugs is well documented in vitro but has not been investigated as thoroughly in vivo. In the course of an investigation of the roles of H1 and H2 receptors in histamine-induced adrenocorticotropic hormone (ACTH) release in rats, it was observed that several antidepressants were potent inhibitors of this response. Male Sprague-Dawley rats were injected with test drugs and then with histamine or histamine agonists. Serum ACTH concentrations were determined by radioimmunoassay. ACTH secretion was induced by both H1 and H2 receptor stimulation. Histamine-induced ACTH release was markedly attenuated by several H1 antihistamines, whereas the H2 antagonists were not as effective. The antidepressants imipramine, doxepin, mianserin, desipramine and amitriptyline suppressed histamine-induced ACTH release. However, iprindole and the antianxiety agent diazepam were without effect. ACTH release induced by histamine agonists was also diminished by pretreatment with some of these blocking agents.