Carazolol: a potent, selective β3-adrenoceptor agonist

Carazolol is a β₁/β₂ adrenoceptor antagonist of high potency used in the treatment of hypertension. Its affinity for the β₃-adrenoceptor was determined in Chinese hamster ovary cells transfected with the gene of the human or the murine β₃-adrenoceptor. Carazolol is recognized with a nanomolar affinity, which position it among the best ligands for β₃-adrenoceptors. The adenylyl cyclase stimulation was measured in transfected cells where carazolol acted as a full agonist on both murine and human receptor subtypes. Furthermore, in murine adipocyte-like 3T3-F442A cells, which express β₃-adrenoceptor naturally, carazolol induced lipolysis. This compound also appeared to be a useful tool for molecular characterization of the β₃-adrenoceptor : unlike the classical β₃-adrenoceptor agonists, carazolol conferred an appreciable protection of receptor binding sites against inactivation by the reducing agent dithiothreitol. The major iodinated analog of carazolol retained its binding characteristics for the β₃-adrenoceptor and remained an efficient adenylyl cyclase stimulator in cells expressing human β₃-adrenoceptor.