caa a22 4500 469078499 CHVBK 20180323132942.0 cr unu---uuuuu 170328e19921101xx s 000 0 eng 10.1007/BF00169013 doi (NATIONALLICENCE)springer-10.1007/BF00169013 Electrophysiologic and anticholinergic effects of pirmenol enantiomers in guinea-pig myocardium [Elektronische Daten] [Haruaki Nakaya, Yuiehi Hattori, Masayuki Endou, Satoshi Gandou, Morio Kanno] Summary: Since it has been reported that several class I drugs stereoselectively block sodium channels, potassium channels and muscarinic receptors in cardiac tissues, electrophysiologic and anticholinergic effects of enantiomers of pirmenol, a class I antiarrhythmic drug, were examined. Both (+) and (−) pirmenol depressed the maximum upstroke velocity (Vmax) of the action potential in a concentration-dependent manner in guinea-pig papillary muscles driven at 1.0 Hz, and there was no significant difference in the potency of the class I effect between the enantiomers. The onset rates of use-dependent block (UDB) of (Vmax) at 2.0 Hz for 10 µmol/l (+) and (−) pirmenol were 0.30±0.03 and 0.29±0.01 per action potential, and the recovery time constants from UDB for (+) and (−) pirmenol were 27.0±2.7 and 27.7±1.9 s, respectively, indicating no difference in the binding and unbinding kinetics to the sodium channel between the enantiomers. Both (+) pirmenol and (−) pirmenol prolonged action potential duration (APD) at low concentrations (1-10 µmol/l) and shortened it at high concentrations (30-100 µmol/l) Again, there was little difference with respect to the effects on APD between the enantiomers. However, in the isolated guinea-pig left atria (−) pirmenol more potently antagonized the negative inotropic effect of carbachol than (+) pirmenol, and the pA2 values for (+) and (−) pirmenol were 6.41 and 6.71, respectively. The functional study was supported by the radioligand binding experiments using [3H]N-methyl scopolamine ([3H]NMS) in guinea-pig left atrial membranes. Specific ([3H]NMS) binding was competitively displaced by the enantiomers, and the apparent dissociation constant for (+) pirmenol (1.95±0.23 µmol/l) was significantly greater than that for (−) pirmenol (0.90±0.18 µmol/l). These results suggest that pirmenol enantiomers stereoselectively interact with cardiac muscarinic receptors but not so with cardiac sodium and potassium channels. Springer-Verlag, 1992 Pirmenol nationallicence Stereoselectivity nationallicence Muscarinic receptors nationallicence Sodium channel nationallicence Potassium channel nationallicence Use-dependent block nationallicence Nakaya Haruaki Department of Pharmacology, Hokkaido University School of Medicine, 060, Sapporo, Japan aut Hattori Yuiehi Department of Pharmacology, Hokkaido University School of Medicine, 060, Sapporo, Japan aut Endou Masayuki Department of Pharmacology, Hokkaido University School of Medicine, 060, Sapporo, Japan aut Gandou Satoshi Department of Pharmacology, Hokkaido University School of Medicine, 060, Sapporo, Japan aut Kanno Morio Department of Pharmacology, Hokkaido University School of Medicine, 060, Sapporo, Japan aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/5(1992-11-01), 555-562 0028-1298 346:5<555 1992 346 210 https://doi.org/10.1007/BF00169013 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00169013 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nakaya Haruaki Department of Pharmacology, Hokkaido University School of Medicine, 060, Sapporo, Japan aut NATIONALLICENCE 700 1- Hattori Yuiehi Department of Pharmacology, Hokkaido University School of Medicine, 060, Sapporo, Japan aut NATIONALLICENCE 700 1- Endou Masayuki Department of Pharmacology, Hokkaido University School of Medicine, 060, Sapporo, Japan aut NATIONALLICENCE 700 1- Gandou Satoshi Department of Pharmacology, Hokkaido University School of Medicine, 060, Sapporo, Japan aut NATIONALLICENCE 700 1- Kanno Morio Department of Pharmacology, Hokkaido University School of Medicine, 060, Sapporo, Japan aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/5(1992-11-01), 555-562 0028-1298 346:5<555 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer