TY - JOUR
T1 - Antitachycardiac effect of OPC-8212, a novel cardiotonic agent, on tachycardiac responses of guinea pig isolated right atria to isoproterenol and histamine
AU - Yanagisawa, Teruyuki
AU - Ishii, Kuniaki
AU - Taira, Norio
PY - 1987/7
Y1 - 1987/7
N2 - In isolated right atria of guinea pigs, OPC-8212 produced a concentration-dependent decrease in spontaneous beating rate that had previously been elevated by isoproterenol or histamine in the presence of nadolol. OPC-8212 scarcely affected the baseline rate, however, OPC-8212 depressed the maximum increase in right atrial rate induced by isoproterenol or histamine in the presence of nadolol. These effects of OPC-8212 were discernible from the effects of its solvent sulfolane. We propose the term "antitachycardiac" to describe such effects of OPC-8212 to distinguish it from those of bradycardic agents. When the concentration-response curves of isoproterenol or histamine for positive chronotropy were normalized, these curves were shifted in a parallel way to the left with OPC-8212, indicating that OPC-8212 retains activity as a cyclic AMP phosphodiesterase inhibitor. The virtual absence of the chronotropic effect of OPC-8212 on the baseline rate and the antitachycardiac effect are discussed in terms of the opposing effects in increasing the inward calcium current on one hand and in decreasing the outward potassium and the inward current activated by hyperpolarization on the other.
AB - In isolated right atria of guinea pigs, OPC-8212 produced a concentration-dependent decrease in spontaneous beating rate that had previously been elevated by isoproterenol or histamine in the presence of nadolol. OPC-8212 scarcely affected the baseline rate, however, OPC-8212 depressed the maximum increase in right atrial rate induced by isoproterenol or histamine in the presence of nadolol. These effects of OPC-8212 were discernible from the effects of its solvent sulfolane. We propose the term "antitachycardiac" to describe such effects of OPC-8212 to distinguish it from those of bradycardic agents. When the concentration-response curves of isoproterenol or histamine for positive chronotropy were normalized, these curves were shifted in a parallel way to the left with OPC-8212, indicating that OPC-8212 retains activity as a cyclic AMP phosphodiesterase inhibitor. The virtual absence of the chronotropic effect of OPC-8212 on the baseline rate and the antitachycardiac effect are discussed in terms of the opposing effects in increasing the inward calcium current on one hand and in decreasing the outward potassium and the inward current activated by hyperpolarization on the other.
KW - Antitachycardiac agent
KW - Cardiotonic agent
KW - Guineapig right atria
KW - Histamine
KW - Isoproterenol
KW - OPC-8212
UR - http://www.scopus.com/inward/record.url?scp=0023198843&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023198843&partnerID=8YFLogxK
U2 - 10.1097/00005344-198707000-00007
DO - 10.1097/00005344-198707000-00007
M3 - Article
C2 - 2441153
AN - SCOPUS:0023198843
VL - 10
SP - 47
EP - 54
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 1
ER -