Methoctramine selectively blocks cardiac muscarinic M2 receptors in vivo.

The antimuscarinic effects of methoctramine (N, N'-bis[6-[(2-methoxybenzyl)amino]hexyl]-1, 8-octanediamine tetrahydrochloride), a polymethylene tetraamine endowed with high cardioselectivity in vitro, were assessed in two in vivo preparations. Methoctramine (300 micrograms/kg i.v.) strongly inhibited the methacholine- and muscarine-induced bradycardia in the anaesthetized an pithed rat, respectively. The same dose of methoctramine did not significantly affect the depressor action of methacholine in the anaesthetized rat mediated by vascular M2 receptors. Furthermore, even high doses of methoctramine (up to 1 mg/kg i.v.) did not reduce the ganglionic M1 receptor-mediated tachycardia and pressor response to muscarine or McN-A-343 in the pithed rat. These data suggest that methoctramine while showing high affinity for cardiac M2 alpha receptors has rather low affinity for ganglionic M1 and vascular M2 receptors. This in vivo study thus provides further evidence to support the view that methoctramine is a potent and highly selective antagonist of cardiac M2 alpha receptors.