The Clinical Pharmacology of Metocurine: Dimethyltubocurarine Revisited

Abstract

The clinical pharmacology of metocurine (formerly dimethyltubocurarine) was studied in 55 patients. Evoked force of thumb adduction was measured at 0.15 Hz during nitrous oxide-morphine-thiopental anesthesia. The ED50 and ED95 for twitch inhibition were 0.13 and 0.28 mg/kg. The dose-response curve did not differ significantly from parallelism with curves for pancuronium and d-tubocurarine. Potency ratios were 0.25 and 1.8 vs. pancuronium and d-tubocurarine. The speed of onset and the duration of metocurine-induced block at high dosage employed for tracheal intubation did not differ significantly from the corresponding values obtained for approximately equipotent doses of pancuronium and d-tubocurarine. Metocurine, 0.3 mg/kg, produced 96.1% mean twitch depression within 4.8 .+-. 0.6 (SEM) [Standard Error of the Means] min. Recovery to 25% of the control twitch height took 82.4 .+-. 12.0 (SEM) min at this dose. Doses in the range 0.2-0.3 mg/kg are recommended for the production of abdominal relaxation during NO2-narcotic-thiopental anesthesia. Jaw relaxation was sufficient at 0.3 mg/kg for smooth tracheal intubation in 13 of 15 patients. Neostigmine antagonism of metocurine-induced block required dosage and timing similar to those of d-tubocurarine and pancuronium. Metocurine produced no significant change in heart rate or mean arterial pressure in doses as high as 0.3 mg/kg. At o.4 mg/kg, heart rate increased 18% and arterial pressure decreased 6.3%. These changes were statistically significant but generally not clinically important and reflect a short-lasting (5-10 min) response suggestive of histamine release, which occurred in 6 of 18 subjects who received this dose.