Local anaesthetic activity of vesamicol in the electric organ of Torpedo.

Synaptic transmission in intact pieces of the Torpedo electric organ treated with vesamicol (2-(4-phenylpiperidino)cyclohexanol, formerly AH5183) was elicited by trains of repetitive electrical stimulation at different frequencies. When the frequency of stimulation was increased from 10 to 50 or 100 Hz, micromolar concentrations of vesamicol enhanced the tetanic rundown of the successive tissue responses. This effect was already detectable with 10 microM vesamicol. It was dramatically potentiated with concentrations of 50 or 100 microM vesamicol, which caused complete failure of transmission after usually less than 10 responses. The drug was unequivocally demonstrated to act by depressing the evoked release of acetylcholine as a consequence of a highly frequency- and concentration-dependent impairment of Na+ channel function in afferent axons. It is concluded that, in the electric organ, vesamicol blocks transmission by acting as a local anaesthetic. This action of micromolar concentrations of vesamicol must be taken into account especially during high-rate nerve activity.