Neuromuscular Blocking Actions of Hexamethonium, Rocuronium and (-)Vesamicol

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 32℃ 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 1μM for R, and 19.4, 15.2 and 13.3μM 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. (Korean J Anesthesiol 2007; 52: 681~6)

[1]  O. Larsson,et al.  Distinct Pharmacologic Properties of Neuromuscular Blocking Agents on Human Neuronal Nicotinic Acetylcholine Receptors: A Possible Explanation for the Train-of-four Fade , 2006, Anesthesiology.

[2]  H. Kilbinger,et al.  Presynaptic nicotine receptors mediating a positive feed-back on transmitter release from the rat phrenic nerve , 1986, Naunyn-Schmiedeberg's Archives of Pharmacology.

[3]  H. Kilbinger,et al.  Release of [3H]acetylcholine from a modified rat phrenic nerve-hemidiaphragm preparation , 1986, Naunyn-Schmiedeberg's Archives of Pharmacology.

[4]  Y. Adachi,et al.  Presynaptic inhibitory effects of rocuronium and SZ1677 on [ 3 H ]acetylcholine release from the mouse hemidiaphragm preparation , 2002, Neurochemistry International.

[5]  R. Parsons,et al.  Empty synaptic vesicles recycle and undergo exocytosis at vesamicol-treated motor nerve terminals. , 1999, Journal of neurophysiology.

[6]  A. England,et al.  The Effect of Rate of Stimulation on Force of Contraction in a Partially Paralyzed Rat Phrenic Nerve Hemidiaphragm Preparation , 1997, Anesthesia and analgesia.

[7]  S. Parsons,et al.  The pharmacology of vesamicol: an inhibitor of the vesicular acetylcholine transporter. , 1992, General pharmacology.

[8]  S. Bevan,et al.  Modes of hexamethonium action on acetylcholine receptor channels in frog skeletal muscle , 1991, British journal of pharmacology.

[9]  T. Searl,et al.  The effects ofl-vesamicol, an inhibitor of vesicular acetylcholine uptake, on two populations of miniature endplate currents at the snake neuromuscular junction , 1990, Neuroscience.

[10]  M. Gallacci,et al.  Mechanisms of hexamethonium-induced tetanic fade in the isolated rat muscle. , 1990, Archives internationales de pharmacodynamie et de therapie.

[11]  M. Rk,et al.  Tetanic fade following administration of nondepolarizing neuromuscular blocking drugs. , 1989 .

[12]  S.J. Hong,et al.  Reversals of the neostigmine‐induced tetanic fade and endplate potential run‐down with respect to the autoregulation of transmitter release , 1988, British journal of pharmacology.

[13]  Enomoto Koh-ichi.  Post- and presynaptic effects of vesamicol (AH5183) on the frog neuromuscular junction. , 1988 .

[14]  S. Hong,et al.  Dissociation of the end-plate potential run-down and the tetanic fade from the postsynaptic inhibition of acetylcholine receptor by α-neurotoxins , 1987, Experimental Neurology.

[15]  A. Gibb,et al.  Nicotinic antagonists produce differing amounts of tetanic fade in the isolated diaphragm of the rat , 1986, British journal of pharmacology.

[16]  S.J. Hong,et al.  Mechanisms of the inhibition by neostigmine of tetanic contraction in the mouse diaphragm , 1986, British journal of pharmacology.

[17]  R. Micheroli,et al.  On the neurotrophic control of acetylcholine receptors at frog end‐plates reinnervated by the vagus nerve. , 1985, The Journal of physiology.

[18]  R. M. Jones,et al.  Factors affecting train-of-four fade. , 1985, British journal of anaesthesia.

[19]  J. Byrne,et al.  Effects of hexamethonium and decamethonium on end-plate current parameters. , 1981, Molecular pharmacology.

[20]  W. Bowman.  Prejunctional and Postjunctional Cholinoceptors at the Neuromusclar Junction , 1980, Anesthesia and analgesia.

[21]  A. Harvey,et al.  Antibiotic-induced Paralysis of the Mouse Phrenic Nerve–Hemidiaphragm Preparation, and Reversibility by Calcium and by Neostigmine , 1978, Anesthesiology.

[22]  Corrado Ap,et al.  Competitive antagonism between calcium and antibiotics at the neuromuscular junction. , 1978 .

[23]  W. Bowman,et al.  TETANIC FADE DURING PARTIAL TRANSMISSION FAILURE PRODUCED BY NON‐DEPOLARIZING NEUROMUSCULAR BLOCKING DRUGS IN THE CAT , 1976, Clinical and experimental pharmacology & physiology.

[24]  C. Ferry,et al.  An anti‐curare effect of hexamethonium at the mammalian neuromuscular junction , 1973, British Journal of Pharmacology.

[25]  L. Blaber,et al.  The prejunctional actions of some non‐depolarizing blocking drugs , 1973, British journal of pharmacology.

[26]  G. P. Levy,et al.  The neuromuscular blocking action of 2-(4-phenylpiperidino) cyclohexanol (AH 5183). , 1969, European journal of pharmacology.