Effect of meclastine, a selective H1 receptor antagonist, upon ACTH release

To elucidate further the role of histamine in the control of ACTH secretion we investigated the effect of the selective H1 receptor antagonist meclastine on the ACTH response to insulin hypoglycaemia and to metyrapone-induced hypocortisolaemia in normal subjects. Intravenous meclastine (4.8 mg/90 min) significantly inhibited the hypoglycaemia-induced ACTH and cortisol increase whereas serum GH and PRL concentrations were unaffected. Orally administered meclastine (3 X 2 mg) also reduced the ACTH feedback response to cortisol deficiency in a modified metyrapone test, compared to a placebo. Our findings support the concept of an excitatory influence of histamine upon ACTH secretion via H1 receptors, possibly by stimulation of CRF release.