Effects of mescaline and some of its analogs on cholinergic neuromuscular transmission

Mescaline and two of its analogs, anhalinine and a methylenemescaline trimer, block neuromuscular transmission in frog muscle and affect rat brain tissue. The compounds reduce both directly and nerve-evoked muscle twitches, with a stronger effect on nerve-evoked responses. They decrease the size of endplate potentials, reduce the amount of acetylcholine released per nerve impulse, hyperpolarize the resting membrane potential, and lengthen the action potential. At concentrations that block transmission, they do not displace alpha-bungarotoxin binding to nicotinic receptors, indicating the block is not due to receptor antagonism. The findings suggest mescaline and its analogs inhibit transmission primarily by reducing acetylcholine release and also by altering potassium conductance.

Study at a glance

Abstract

Mescaline (3,4,5-trimethoxyphenylethylamine; MES) and its analogs, anhalinine (ANH) and methylenemescaline trimer (MMT) were investigated, using sciatic-sartorius preparations of the frog and cortical tissue from the rat. The effects of MES and its analogs were examined with respect to muscle twitch, resting membrane potential and nicotinic receptor binding. Mescaline and its analogs (10-100 microM) blocked both directly and neurally evoked twitches but their effects on neurally evoked twitches were greater than those on directly evoked twitches. Mescaline, ANH and MMT decreased amplitude of the miniature endplate and endplate potentials, decreased acetylcholine (ACh) quantal content, hyperpolarized the resting membrane potential and prolonged duration of the action potential. They did not significantly displace the binding of [125I]-alpha-bungarotoxin (alpha-BTX) to nicotinic receptors, at concentrations which blocked neuromuscular transmission. These results suggest that MES and its analogs inhibit cholinergic neuromuscular transmission by blocking release of ACh; they also affect K+ conductance.