Effect of clonidine on neuromuscular transmission and the nicotinic acetylcholine receptor

The effects of clonidine on neuromuscular transmission were investigated in the mouse phrenic nerve-diaphragms and chicken biventer cervicis. Clonidine inhibited the indirect twitch response dose-dependently and reversibly without an effect on the direct response of the muscles to electrical stimulation and KCl. This effect was antagonized effectively by diaminopyridine but not by yohimbine, phentolamine or physostigmine. The quantal content was not affected although the amplitudes of end-plate potential (epp) and spontaneous miniature epp (mepp) were markedly depressed. Clonidine also decreased the slope of the ACh dose-response curve and maximal response in denervated mouse diaphragms as well as the carbachol response in the chinck muscle. In the latter, ACh response was not depressed by clonidine probably because of its inherent anticholinesterase activity. Clonidine facilitated the fading of ACh-contracture either in mouse or chick muscle. It is concluded that clonidine impairs the neuromuscular transmission by a noncompetitive blockade of ACh receptors, most likely affecting the ACh channel but not the recognition site of the ACh receptor. Its inhibitory effect is not mediated by alpha 2-adrenoceptor, suggesting that there is no alpha 2-adrenoceptor on the motor nerve terminal to modulate the transmitter release.