A novel muscarinic receptor antagonist AF-DX 116 differentially blocks slow inhibitory and slow excitatory postsynaptic potentials in the rabbit sympathetic ganglia

Abstract

Muscarinic, slow postsynaptic potentials (s-epsp and s-ipsp) in the rabbit superior cervical ganglia were shown to be differentially depressed by a novel cardioselective M 2-type antagonist AF-DX 116: it antagonized the s-ipsp with IC 50 value of 1.5 × 10 −7M, which is 16-fold more potent in depressing the s-ipsp than the s-epsp. A hyperpolarizing component in the biphasic potential changes induced by a muscarinic agonist, methacholine, was selectively eliminated by this antagonist. AF-DX 116 was thus shown to be an useful tool for discriminating the M 2-type muscarinic responses from those of M 1-type in the nervous system.