Impairment of neuromuscular transmission in experimental animal by labetalol

ABSTRACT

Labetalol is an adrenoceptor antagonist which blocks competitively both, alpha 1 and beta adrenoceptors. It was chosen in the present research to study its effect on neuromuscular transmission in experimental animals. Labetalol was found to produce a dose dependent inhibition of acetyl choline induced contraction of the rectus abdominis muscle of the frog with reversal of this inhibitory action by neostigmine. In the isolated rat phrenic nerve diaphragm preparation, labetalol did not affect muscle contraction in response to direct muscle stimulation, but reduced significantly muscle contraction in response to indirect [phrenic nerve] stimulation. In the cat gastrocnemius-sciatic nerve preparation, labetalol in doses of 400 and 800 micro g/kg l.V. did not affect the muscle, but larger doses of 1 and 2 mg/kg l.V. caused a significant reduction in the muscle contraction in response to sciatic nerve stimulation. However, the reduction in muscle contraction in response to sciatic nerve stimulation by tubocurarine was markedly potentiated by prior administration of labetalol in the dose which did not affect the muscle [400 micro g/kg]. Moreover, the reduction in the muscle contraction after labetalol administration in response to phrenic nerve stimulation in the rat phrenic nerve diaphragm preparation or sciatic nerve stimulation in the gastronomies sciatic nerve preparation was found to be partially antagonized by neostigmine, calcium chloride and adrenaline