Effects of m-cholinoceptor antagonists on the neuromuscular junction.

The effects of four m-cholinoceptor antagonists and d-tubocurarine on carbachol- or nicotine-induced contractions of frog rectus abdominus muscle were investigated. The n-cholinoceptor-mediated contractile responses of frog rectus abdominis muscles were inhibited competitively by d-tubocurarine whereas m-cholinoceptor antagonists inhibited them noncompetitively. Antagonistic potencies for m-cholinoceptor antagonists, assessed by pD'2 values, indicated a rank order of potency which was 4-DAMP > AF-DX 116 > atropine > pirenzepine. The antagonistic potencies of m-cholinoceptor antagonists on electrically induced twitch responses of rat phrenic nerve-diaphragm preparation were also examined. These responses were blocked by 4-DAMP, but pirenzepine had no effect. However, they were enhanced by AF-DX 116 or atropine. Inhibitory action of 4-DAMP in this preparation was suggested to be due to noncompetitive blockade of postjunctional n-cholinoceptors.