We studied the inhibition of fetal (gamma-nAChR) and adult (epsilon-nAChR) 
muscle-type nicotinic acetylcholine receptors by the two new nondepolarizing 
muscle relaxants (NDMRs) rocuronium and rapacuronium, the metabolite 3-desacetyl 
rapacuronium (Org 9488), and five other, longer-used NDMRs (pancuronium, 
vecuronium, mivacurium, d-tubocurarine, and gallamine). Receptors were expressed 
in Xenopus laevis oocytes by cytoplasmic injection of subunit complementary 
RNAs. Functional channels were activated with 10 microM acetylcholine, alone or 
in combination with various concentrations of the NDMRs. Currents were recorded 
with a whole-cell two-electrode voltage clamp technique. All NDMRs reversibly 
inhibited acetylcholine-activated currents in a dose-dependent fashion. 
Potencies of rapacuronium and Org 9488 were not statistically different at 
either gamma-nAChR (half-maximal response = 58.2 and 36.5 nM, respectively) or 
epsilon-nAChR (half-maximal response = 80.3 and 97.7 nM, respectively). The rank 
order of potencies at the epsilon-nAChR (pancuronium > vecuronium similar 
mivacurium > rocuronium similar d-tubocurarine > rapacuronium similar Org 9488 > 
gallamine) correlated highly with the clinical doses needed to produce 50% 
twitch depression at the adductor pollicis muscle in adults. Neuromuscular 
blockade by rapacuronium may be enhanced by its metabolite Org 9488. Different 
drug-receptor affinities of the tested NDMRs contribute to the differences in 
clinical dose requirements of these drugs needed to achieve appropriate muscle 
relaxation.
IMPLICATIONS: Potencies of nondepolarizing muscle relaxants, studied at muscle 
nicotinic acetylcholine receptors expressed in a recombinant expression system, 
correlate highly with the clinical doses needed in adults to produce 50% twitch 
depression at the adductor pollicis muscle.