[Mechanism of action of oxyfedrine as a partial beta receptor agonist].
To investigate a possible dual action of oxyfedrine on beta-adrenergic receptors, hemodynamics and systolic time intervals were studied in 12 healthy volunteers during intravenous infusion of isoprenaline. The dose was titrated to a mean target heart rate of 113 bpm corresponding to an average dose of 6.16 micrograms/min. After return to baseline hemodynamics, oxyfedrine was administered as an intravenous bolus of 8 mg and the protocol was repeated. Compared to baseline, the percentage changes induced by isoprenaline at doses of 2.73 and 6.16 micrograms/min before and after (in parentheses) oxyfedrine were: heart rate: +33/+83% (+19/+62%); cardiac output: +90/153% (+30/+71%); systolic blood pressure: +16/+20% (+6/+7%); stroke volume: +42/+38% (+10/+6%); peripheral vascular resistance: -50/-63% (-31/-50%); cardiac work: +86/+148% (+19/+54%); pre-ejection period: -40/-56% (-27/-45%); isovolumic contraction time: -56/-79% (-29/-63%); systolic ejection rate: +67/+103% (+27/+52%); tension time index: +32/+50% (+7/+20%). Thus, the dose-dependent hemodynamic effects of isoprenaline were significantly attenuated by oxyfedrine pre-treatment with a shift of the dose-response curve to the right; this was attributed to a beta-antagonistic property of oxyfedrine. The results indicate that, in view of its well-known beta-stimulating effects, oxyfedrine exerts a dual action on adrenergic beta-receptors consistent with partial agonistic activity. Thereby, the different profiles of hemodynamic and metabolic actions of oxyfedrine compared to those of pure beta-agonistic agents can be explained as well as its beneficial therapeutic effects in patients with coronary heart disease.
D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000294:innervation*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010099:Oxyfedrine / Q000494:pharmacology*; D011427:Propiophenones / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects
D011427:Propiophenones; D011943:Receptors, Adrenergic, beta; D010099:Oxyfedrine; D007545:Isoproterenol
Zum Wirkmechanismus von Oxyfedrin als partieller Betarezeptorenagonist.