Abstract:
The neuromuscular blocking activity of
l-curine, homoaromoline,
d-tetrandrine and
d-chondrodendrine isolated from the root of
Cyclea barbata Miers in Hai-nan Island was studied. In rabbits the head-drop test showed that the quaternary salts of
l-curarine and homoaromoline were more potent than the other two alkaloids. Dimethyl
l-curine dimethiodide or dimethochloride derivatives were prepared and examined in conscious rabbits, mice, rats, cats and dogs. It was found that the dimethyl derivatives were about 1.5~3 times stronger than the parent compound and were 0.5~4 times more active than tubocurarine except in rats. In sciatic-tibialis preparations of anaesthetized rabbits, the neuromuscular block produced by
l-curine and its derivatives or homoaromoline was readily reversed by neostigmine, antagonized by suxamethonium and augmented by tubocurarine. Tetanus was poorly sustained during its partial block, and the post-tetanus twiching were temporarily increased in amplitude. In conscious chicks it produced a flaccid paralysis. The results indicate that the quaternary salts of these three compounds are nondepolarizing blocking drugs like tubocurarine. In threefold neuromuscular blocking doses,
l-curine and its dimethyl derivative all produced hypotension in anaesthetized cats and dogs and released histamine in anaesthetized dogs, but these effects were less potent than tubocurarine. In contrast to tubocurarine, its ganglion blocking effects were absent. In conscious and artificially ventilated rabbits,
l-curine or dimethyl
l-curine at 40~50 times the head-drop dose produced no marked changes in EGG. In rabbits sacrificed 48~72 hours after successive injection of 5~10 times head-drop dose of
l-curine or dimethyl
l-curine, no obvious pathological change in various tissues was found. In mice and rats,
l-curine and dimethyl
l-curine had a higher therapeutive index than tubocurarine.