The neuromuscular blocking effects of Org 9426, the 2-morpholino, 16-allyl-pyrrolidino derivative of the 3-desacetoxy analogue of vecuronium have been investigated in anaesthetized patients. Based on data from a pilot study, two doses, 250 and 500 micrograms kg-1 (estimated as the ED90 and 2 x ED90, respectively) were chosen. Org 9426 appeared to be six to eight times less potent than vecuronium and showed a faster rate of development of neuromuscular block, with good to excellent intubation conditions within 60 s after administration of a dose of 500 micrograms kg-1. The duration of action and the recovery index appeared to be similar to those of vecuronium. Side effects were not noted. Org 9426 may have advantages over existing non-depolarizing neuromuscular blocking agents with respect to rate of development of good intubating conditions, and is stable in aqueous solutions.

The pharn~acodynamics and pharmacokinelics oJ" a new nondepolarizing neuromuscular blocking agent, Ore 9426, were investigated. Ten patients undergoing elective head and neck surgery and anaesthetized with nitrous oxide', halothane and fentanyl, received a bolus dose of Ore 9426 (I rag. kg -t , 3 x EDgo

The neuromuscular blocking effects of the new monoquaternary analogue of pancuronium, Org NC 45, have been investigated in anaesthetized patients. In different doses administered as a single i.v. bolus or as an initial bolus followed by several small maintenance doses or by a continuous infusion. Org NC 45 appears to be approximately as potent as pancuronium, but has a more rapid onset of action, considerably shorter duration of action and faster recovery rate than pancuronium. It showed no cumulative effects even after 10 maintenance doses were injected in succession. Doses of 0.08 mg kg-1 provided ideal intubating conditions in 90--95 s. Infusions of Org NC 45 provided much smoother control of neuromuscular blockade than did pancuronium. No cardiovascular side-effects were noted even at the greatest dose (0.12 mg kg-1) used. Org NC 45 has clear advantages over pancuronium and represents a potentially valuable addition to the armamentarium of clinically useful muscle relaxants.

No abstract

Nine healthy subjects (7 men; 2 women) received single 20-mg IV injections of 4-aminopyridine (4-AP). Six of the subjects received the same dose in the form of enteric-coated tablets and four the same dose in uncoated tablets; treatments were at least 2 wk apart. Blood, saliva, and urine were assayed for 4-AP using a high-performance liquid chromatography. Kinetic analysis of serum concentrations after intravenous dosing resulted in the best fitting of a triexponential model in five and a biexponential model in four subjects. The apparent volume of distribution (V) was 2.6 +/- 0.9 (mean +/- SD) 1 kg-1, the terminal half-life (t 1/2) 3.6 +/- 0.9 hr, and the total serum clearance 0.61 +/- 0.14 1 hr-1 kg-1. Saliva concentrations were higher than those in serum after 5 min, with a mean correlation coefficient of 0.989 (n = 5). The t 1/2 and V calculated from serum and saliva concentrations were of the same order. The total urinary excretion of unchanged 4-AP was 90.6 +/- 7.8% after intravenous doses and 88.5 +/- 4.8% after oral doses of enteric-coated tablets. The bioavailability of the enteric-coated tablets calculated from the area under the serum concentration curve (95 +/- 29%) did not differ from that calculated from urinary excretion (98 +/- 8%). Protein binding of 4-AP was found to be negligible. Biotransformation is unlikely.