Cimetidine, a histamine H2 receptor antagonist, occupies androgen receptors

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.