Effects of optical isomers of ephedrine and methylephedrine on the twitch response in the isolated rat vas deferens and the involvement of alpha 2-adrenoceptors.
The effects of optical isomers of ephedrine (EPH) and methylephedrine (MEP) on the twitch response to electrical stimulation (1 msec, 1 Hz) in the isolated rat vas deferens were investigated to clarify the action on alpha 2-adrenoceptors. l-EPH (10(-7) 3 x 10(-5) M) and d-EPH (10(-6)-10(-4) M) markedly inhibited the twitch response in the presence of prazosin (10(-6) M). l-MEP also inhibited the twitch response at high concentrations (3 x 10(-5)-10(-3) M). The rank order of inhibitory potency was 1-EPH > d-EPH >> l-MEP. Yohimbine (3 x 10(-7) M), a selective alpha 2-adrenoceptor antagonist, attenuated the twitch-inhibitory effects of EPH isomers and l-MEP. Furthermore, the twitch-inhibitory effects of EPH isomers and l-MEP were attenuated by reserpine treatment (8 mg/kg, s.c.). On the other hand, d-MEP showed the potentiation of twitch response, and competitively antagonized the twitch-inhibitory effect of clonidine (10(-9)-10(-6) M) with the pA2 value of 4.3 in the presence of prazosin. The results suggest that EPH isomers and l-MEP have stimulating activity for presynaptic alpha 2-adrenoceptors. In addition, the twitch-inhibitory effect of EPH isomers and l-MEP may be at least partly mediated through the release of noradrenaline. It is also suggested that d-MEP has competitive alpha 2-adrenoceptor antagonist activity.
Toyama Prefectural Institute for Pharmaceutical Research, Japan.
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Kawasuji
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Koike
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Saito
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D003000:Clonidine / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004809:Ephedrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D014649:Vas Deferens / Q000187:drug effects
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; C041707:N-methylephedrine; D004809:Ephedrine; D003000:Clonidine; D009638:Norepinephrine