The electrophysiological effects of opioid receptor-selective antagonists on sheep Purkinje fibres.
The cardiac electrophysiological effects of 16-methylcyprenorphine (M8008), nor-binaltorphimine (NBT) and naltrexone, which are relatively specific opioid antagonists for delta, kappa and mu receptors, respectively, were studied in paced (1.5 Hz) sheep Purkinje fibres in vitro. M8008 (1 ng ml-1-10 micrograms ml-1) caused a concentration-dependent reduction in the maximum rate of depolarisation of phase 0 (MRD) and in the action potential duration measured at 50% repolarisation, APD50. Neither NBT (10 ng ml-1-10 micrograms ml-1) nor naltrexone (1 ng ml-1-10 micrograms ml-1) produced any significant effect on the cardiac action potential. In the presence of a physiological salt solution modified to mimic some of the changes that occur during myocardial ischaemia (i.e. hypoxia, acidosis, hyperkalaemia), M8008 caused a more marked reduction in MRD and prolonged rather than shortened APD50. These results suggest that the reported antiarrhythmic activity of M8008, but not NBT or naltrexone, may be, at least in part, explained by a direct cardiac electrophysiological action.
McIntosh
M
M
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, U.K.
Kane
K
K
Parratt
J
J
D000138:Acidosis / Q000503:physiopathology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology; D006947:Hyperkalemia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D009019:Morphinans / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects*; D012756:Sheep
D009019:Morphinans; D009292:Narcotic Antagonists; C051844:norbinaltorphimine; C051207:16-methylcyprenorphine; D009271:Naltrexone