ABSTRACT
BACKGROUND: Hexamethonium (HM) and Rocuronium (R) are nAChR antagonists. However, there is some controversy as to whether R has a selective presynaptic effect. (-)Vesamicol (V) inhibits the transport of acetylcholine into the vesicles. This study compared the neuromuscular blockade of HM, R and V. METHODS: Hemidiaphragm-phrenic nerve preparations (male Sprague-Dawley rats [150-250 g]) were bathed in a Krebs solution maintained at 32oC and aerated with a mixture of 95% O2 and 5% CO2. Isometric forces were generated in response to 0.1 Hz, and 1.9-second 50 Hz with supramaximal stimulation (0.2 ms, rectangular) of the phrenic nerve. HM, R and V were added sequentially to achieve an 80-90% decrease in the ST. The ECs for ST, PTT and TF were calculated using a probit model. The antagonism indices of calcium (5 mM) and neostigmine (N) (250 nM) were assessed at the 85+/-5% level. RESULTS: The potency of ST, PTT and TF were respectively, 5.92, 3.56 and 1.99 mM for HM, 10.81, 5.27 and 4.4 1micronM for R, and 19.4, 15.2 and 13.3micronM for V. The neuromuscular blockades of R were reversed by N but not by calcium. Those of V were not reversed by either of them. Calcium and N inhibited the decrease in ST and TF by HM, respectively. CONCLUSIONS: The mechanism for how HM and R affect the neuromuscular blockade are different. V might not affect the release of acetylcholine.