Cimetidine, a Histamine H2Receptor Antagonist, Occupies Androgen Receptors*

Abstract

The histamine H2 receptor antagonist cimetidine is in increasing usage in the medical management of peptic ulcer. In clinical trials, its most frequent side effect is gynecomastia. Such estrogenic/antiandrogenic manifestations are well known side effects of treatment with digitoxin or spirolactones. Both of these drugs share a common skeleton with the steroid hormones and have been shown to occupy estrogen and/or androgen receptors. Cimetidine has no measurable affinity for rat uterine estradiol receptors, but competes for tritiated dihydrotestosterone-binding sites in mouse kidney preparations with a displacement curve parallel to that for unlabeled dihydrotestosterone. Steroid receptor-mediated side effects, therefore, may not be confined to molecules with a common skeleton, such as steroids, spirolactones, and cardiac glycosides, but may extend to such apparently unrelated molecules as histamine antagonists and androgens.