An anti‐curare effect of hexamethonium at the mammalian neuromuscular junction

Abstract

1 Experiments were performed on the isolated phrenic nerve and diaphragm preparation of the rat. 2 In preparations partly blocked with (+)-tubocurarine, the twitch amplitude increased after hexamethonium. This enhancement was not seen in preparations partly blocked with Mg⁺⁺ or with gallamine. High concentrations of hexamethonium produced failure of contraction. 3 Extracellular endplate potentials were recorded from blocked preparations. The administration of hexamethonium resulted in an increased amplitude of these potentials only in curarized muscle. 4 Hexamethonium had no anticholinesterase activity nor did it depolarize muscle cells or increase the quantal release of transmitter. 5 It is concluded that hexamethonium exerts a specific anti-curare action. Experiments on the recovery of the twitch after washing out antagonists indicate that this process is limited by diffusion. The difference in rates of diffusion of hexamethonium and (+)-tubocurarine does not account for their interaction. The basis of the anti-curare action of hexamethonium is discussed.