Chronotropic Effects of Optical Isomers of Ephedrine and Methylephedrine in the Isolated Rat Right Atria and in Vitro Assessment of Direct and Indirect Actions on β_1-Arenoceptors

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Effects of optical isomers of ephedrine (EPH) and methylephedrine (MEP) on the spontaneous beating rate of isolated right atrium of normal and reserpinized rat were investigated to assess direct and indirect actions on β_1-adrenoceptors. l-EPH (3×10^<-7>-3×10^<-5>M) and d-EPH (10^<-6>-10^<-4>M) markedly increased beating rate of rat right atrium. l-MEP (10^<-5>-3×10^<-4>M) showed slight increase in heart rate. The potency of positive chronotropic effect is l-EPH>d-EPH≫l-MEP. l-EPH was about 3 times as potent as d-EPH. In addition, d-MEP (3×10^<-5>-3×10^<-4>M) caused a decrease in heart rate. Positive chronotropic effects of EPH isomers and l-MEP were attenuated by pretreatment with atenolol (a selective β_1-adrenoceptor antagonist) or reserpine treatment (8 mg/kg, s.c.). In reserpinized atria, the maximal increase by d-EPH was quite small, and l-MEP decreased heart rate. On the other hand, d-MEP, at 3×10^<-4>M, did not show antagonist activity against the positive chronotropic effect of isoprenaline (10^<-10>-10^<-5>M). These results suggest that l-EPH, d-EPH and l-MEP have β_1-adrenoceptor agonist activity, while d-MEP is suggested to have only low or no affinity for β_1-adrenoceptors. The relatively weak activity of l-MEP is believed to be mainly mediated by released noradrenaline. It is also suggested that d-EPH has very potent noradrenaline-releasing activity.
公益社団法人日本薬学会の論文
1996-11-15