ESERINE AND NEOSTIGMINE ANTAGONISM TO D-TUBOCURAINE

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Abstract
The antagonistic effect of eserine and neostigmine to d-tubocurarine was studied on anesthetized and unanesthetized animals. Animals were anesthetized with morphine, Na barbital or by cyclopropane-O2. The peripheral end of the severed sciatic nerve was subjected either to monophasic spike shocks at 5 sec. intervals, or to short bursts of tetanic stimuli at 10 sec. intervals. Slow intraven. injn. of 0.18 mg./kg. of d-tubocurarine decreased or abolished muscle contractions after both types of stimuli. The intraven. injn. of 1 mg. of neostigmine abolished the d-tubocurarine effect more readily in the mono-phasic spike shock expts. than the intraven. injn. of 2 mg. of eserine salicylate. Similarly in the tetanic expts., the intraven. injn. of 0.125 mg./kg. of neostigmine was more effective than the intraven. injn. of 0.125 mg./kg. of eserine salicylate. In unanesthetized animals the recovery time was observed after the intraven. admn. of 120%, 140%, and 160% of the "head-drop" dose without antidote, with 0.125 mg./kg. of eserine + 0.1 mg./kg. of atropine and with 0.05 mg./kg. of neostigmine. Neostigmine was the best antidote and also proved to be superior to mixtures of eserine, atropine, and ephedrine. Neostigmine (0.0167 mg./u. of curare) markedly shortened the duration of respiratory paralysis, "head drop," and ataxia after 3 "head-drop" doses of d-tubocurarine. On the basis of exptl. findings, larger (1.5 to 2.5 mg.) doses of neostigmine are recommended to counteract curare over-dosage in clinical practice.

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