EFFECT OF MECLASTINE, A SELECTIVE H₁ RECEPTOR ANTAGONIST, UPON ACTH RELEASE

Abstract

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.

Quetiapine reduces nocturnal urinary cortisol excretion in healthy subjects

“…Animal and human studies demonstrated reduced cortisol levels after administration of a 1 -adrenergic antagonistic drugs (Laakmann et al 1986;al Damluji 1993). The antihistaminergic drug cyproheptadine inhibits the corticotropin releasing hormone induced ACTH and cortisol release in normal subjects (Allolio et al 1987) and the selective H1 receptor antagonist meclastine inhibits the hypoglycemia-induced ACTH and cortisol increase (Allolio et al 1983).…”

Clemastine, the H1 Histamine Receptor Antagonist, Alters the Human Sex and Thyroid Hormonal Profiles

“…Allolio and his companions [6] studied the effect of the antihistaminic, Meclastine, on ACTH response to insulin hypoglycemia and to metyrapone-based hypocortisolemia in healthy persons. They reported that meclastine administration retracted the hypoglycemia-induced ACTH and cortisol elevation while serum GH and prolactin levels were unchanged.…”

“…Another research group [6] observed significant changes in the adrenocorticotropic hormone (ACTH) secretion levels on antihistaminic drug administration, probably by activation of corticotropin-releasing hormone (CRH) or corticotropin-releasing factor (CRF) release.…”

Altered Methylprednisolone Pharmacodynamics in Healthy Subjects With Histamine N‐Methyltransferase C314T Genetic Polymorphism

“…Previous studies have shown that cortisol and adrenocorticotropic hormone (ACTH) secretions were stimulated by intravenous and intracerebroventricular injection of histamine in animals [29][30][31][32][33] and suggested that these stimulatory effects were mediated via the activation of the H1 and H2 receptors [33][34][35][36] through the induction of corticotrophin releasing hormone (CRH) [37][38][39] and proopiomelanocortin (POMC)-derived peptide expressions. 40 The responses of ACTH to centrally administered histamine, however, were prevented by pretreatment with glucocorticoids, 40 which are known to inhibit POMC mRNA synthesis and expression in the anterior pituitary.…”