The effects of histamine H2 receptor antagonists on androgen action in vivo and dihydrotestosterone binding to the rat prostate androgen receptor in vitro.

Several histamine H2 receptor antagonists have been tested for antiandrogenic activity by determining their effects on accessory sex organ weights in castrate testosterone propionate (TP) treated rats and on [3H] dihydrotestosterone (DHT) binding to the androgen receptor of the rat ventral prostate in vitro. When given in high doses cimetidine and metiamide possessed antiandrogenic activity whereas the other H2 receptor antagonists SK&F 92456, SK&F 92994, SK&F 92629 amd SK&F 93479 did not Cimetidine, metiamide and SK&F 92456 inhibited (3H] DHT binding to rat ventral prostate androgen receptor in vitro whereas SK&F 92629 and SK&F 93479 did not. SK&F 92994 affects DHT binding only slightly. Of the compounds that are similar to cimetidine in their potency as H2 receptor antagonists only metiamide was antiandrogenic. However SK&F 92994 and SK&F 93479 are not antiandrogenic despite being more potent than cimetidine as H2 antagonists. It is concluded that the antiandrogenicity of cimetidine and metiamide was not related to their activity as histamine H2 receptor antagonists.