The pharmacodynamics and pharmacokinetics of the two most recent aminosteroid neuromuscular blocking drugs to become available,
rapacuronium bromide (
Org 9487) and
rocuronium bromide are reviewed. Two new classes of
drug with neuromuscular blocking properties, the bis-tetrahydroisoquinolinium chlorofumarates and the tropinyl diester derivatives are introduced. Comparisons between these drugs and
mivacurium and
cisatracurium are made.
Rapacuronium 1.5 mg kg(-1) (ED95 1 mg kg(-1)), produces maximal neuromuscular block in 54 s. Time to recovery of the train-of-four ratio to 0.7 is achieved within 20 min after neostigmiine 0.05 mg kg(-1) given at 2 min. The plasma clearance of
rapacuronium is 7-8 ml kg(-1) min(-1).
Rapacuronium undergoes hepatic metabolism: no prolongation of effect has been reported after a single bolus or a short infusion in patients with hepatic or
renal failure.
Org 9488 is the 3-desacetyl metabolite of
rapacuronium, which has neuromuscular blocking properties. Its much lower clearance (1.28 ml kg(-1) min(-1)) and plasma equilibration constant (0.105 min(-1)) may limit the prolonged use of
rapacuronium.
Rocuronium given at 2xED95 produces maximal neuromuscular block in 1 min. Spontaneous recovery of the train-of-four ratio to 0.7 takes over 40 min.
Rocuronium has a plasma clearance of 4 ml kg(-1) min(-1). Its pharmacodynamics are altered in hepatic and renal disease. A number of
anaphylactoid reactions to
rocuronium have been reported recently. The bis-tetrahydroisoquinolinium chlorofumarate
GW280430A has an ED95 of 0.19 mg kg(-1). Given at three times this dose, onset of neuromuscular block occurs within 100 s; the duration of block is 8-9 min. Following a 2 h infusion, the recovery index does not seem to be increased. Early studies suggest that this
drug has no adverse cardiovascular or respiratory side-effects. The tropinyl diester derivative
G-1-64 will produce 80-90% neuromuscular block in less than 2 min using 3xED80. Ninety per cent recovery of the first twitch of the train-of-four occurs after 5-7 min using one ED80. A recovery index of less than 2 min has been reported in rats. All the tropinyl diesters appear to produce vagal block.