DEPOLARIZING NEUROMUSCULAR BLOCKING ACTION OF CORYNEINE DERIVED FROM ACONITE ROOT IN ISOLATED MOUSE PHRENIC NERVE-DIAPHRAGM MUSCLES

The mode of the neuromuscular blocking action of coryneine (a quaterna ry ammonium derivative of dopamine) derived from aconite root was inve stigated in isolated phrenic nerve-diaphragm muscles and denervated di aphragm muscles of mice. Coryneine (20-150 mu M) blocked the nerve-evo ked twitch response without affecting the contraction evoked by electr ical stimulation of the muscle. The blocking effect was reversed by ne ostigmine, a cholinesterase inhibitor. The electrical charge-response curve on depolarization produced by iontophoretically applied acetylch oline (ACh) at the endplate regions in normal muscles was shifted to t he right on decreasing the maximal response by 40 mu M coryneine. The double-reciprocal plot revealed that coryneine reduced the apparent af finity of ACh for its receptor on decreasing the maximal response. Cor yneine (20 mu M-2 mM) itself depolarized the endplate membrane and thi s effect was reversibly suppressed by 1 and 5 mu M pancuronium. Coryne ine (30 mu M-10 mM) produced contractions of denervated muscles in a c oncentration-dependent manner and the effects were reduced by 70 nM pa ncuronium. These results indicate that coryneine is a depolarizing age nt and a mixed-type competitive and noncompetitive neuromuscular block er.