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Mode of action of dimethyl l-curine dimethochloride on neuromuscular transmission

	author = {Qin-zhao Yang and Le-ru Lin},
	title = {Mode of action of dimethyl l-curine dimethochloride on neuromuscular transmission},
	journal = {Acta Pharmacologica Sinica},
	volume = {2},
	number = {1},
	year = {2016},
	keywords = {},
	abstract = {The roots of Cyclea barbata from Hainan Island yield an alkaloid, l-curine. Its derivative, dimethyl l-curine dimethochloride (DCD), has been found to possess powerful neuromuscular blocking property comparable to that of d-tubocurarine chloride.
The blocking effects of DCD on neuromuscular transmission in the isolated rat phrenic nerve-diaphragm preparation was studied. DCD rapidly blocked indirectly the elicited muscle twitch without affecting the compound action potential in the phrenic nerve or twitch elicited by direct stimulation.
DCD was compared with d-tubocurarine both in vivo and in vitro. DCD was 3.5 times as potent as d-tubocurarine in the rabbit  head-drop test, but was only 0.4 times as potent as d-tubocurarine on rat phrenic nerve-diaphragm in vitro. DCD 0.5-1.7 microg/ml produced progressive decreases in strength of contraction. This inhibitory effect disappeared soon after the preparation of diaphragm washed with normal solutions. The time to recover from 90% blockade was shorter for DCD than for d-tubocurarine. Neostigmine reversed the blockade induced by DCD to 100% of the control while it reversed comparable blockade induced by d-tubocurarine to only 80% of the control. On the other hand, neostigmine enhanced the amplitude and duration of  the end-plate potential (epp).
Using the rat phrenic nerve-diaphragm preparation, DCD 10(-8) to 10(-6) mg/ml produced no significant change of miniature end-plate potential (mepp). In low concentrations (1.7*10(-5) mg/ml to 1*10(-4) mg/ml) it increased mepp frequency with no effect on mepp amplitude. At higher doses (above 5*10(-4) mg/ml) mepp and epp amplitudes and end-plate sensitivity to Ach were reduced. There was no effect on resting membrane potential of muscle fibers at the drug concentrations studied. These results indicate that DCD produces muscle relaxation by blocking postsynaptic cholinergic receptors.},
	issn = {1745-7254},	url = {}