The Clinical Pharmacology of Metocurine: Dimethyltubocurarine Revisited

The clinical pharmacology of metocurine (formerly dimethyltubocurarine) was studied in 55 ASA class I–II 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 versus 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 per cent mean twitch depression within 4.8 ± 0.6 (SEM) minutes. Recovery to 25 per cent of the control twitch height took 82.4 ± 12.0 (SEM) minutes at this dose. Doses in the range 0.2–0.3 mg/kg are recommended for the production of abdominal relaxation during nitrous oxide–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 found by Katz in previous studies of d-tubocurarine and pancuronium.29329,30 Metocurine produced no significant change in heart rate or mean arterial pressure in doses as high as 0.3 mg/kg. At 0.4 mg/kg, heart rate increased 18 per cent and arterial pressure decreased 6.3 per cent. 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 six of 18 subjects who received this dose.