The cardio-selectivity of himbacine: a muscarine receptor antagonist

Abstract

The antimuscarinic actions of himbacine were compared with those of atropine and/or homatropine on atria, ileum and trachea from guinea-pigs and rat uterus preparations. The antagonism of acetylcholine or carbachol by all the antagonists was competitive on the preparations studied. The pA2 values of himbacine in all smooth muscle preparations were similar (around 7.2) whereas in atria it exhibited about 10-fold higher affinity (pA2 = 8.2). In contrast, both atropine and homatropine had similar affinities for muscarine receptors (pA2 values around 9.1 and 7.2 respectively) in both atria and smooth muscle. It may be concluded from these results that cardiac and smooth muscle muscarine receptors are not homogeneous and that himbacine is a relatively potent and selective antagonist for cardiac receptors. The cardio-selectivity of himbacine supports the concept of heterogeneity of muscarine receptors.