Neurokinin A (NK 2) receptor revisited with SR 48968, a potent non-peptide antagonist

SR 48968, a new non-peptide antagonist of NK 2 receptors, has been tested in a variety of isolated smooth muscle preparations from rats, guinea pigs, rabbits, hamsters and men, in order to assess its selectivity for NK 2 receptors as well as its competitivity and specificity. The compound has been found to be inactive as a stimulant or relaxant in all preparations but to exert a potent, competitive antagonism, particularly in tissues obtained from rabbits (pA 2 9.8–10.3), guinea pigs (10.5), rats (9.4–9.6), men (9.36–9.6) and hamsters (7.45–8.6). SR 48968 is therefore more active on the NK 2A than on the NK 2B receptor subtype and the human receptor is close to the NK 2A subtype. SR 48968 exerts an antagonism of the competitive type and is therefore suitable for receptor classification despite its slow reversibility in vitro. The sensititity of NK 2A receptors to SR 48968 is at least 1000 times higher than those of NK 1 and NK 3 receptors. The compound does not affect the effects of bradykinin, angiotensin or bombesin. Because of its activity in human tissues, its potency and long duration of action, SR 48968 is a new promising pharmacologic and possibly therapeutic agent.