A clinical approach for the identification of peripheral pre- and post-synaptic alpha-adrenergic receptors.
The present study examines the possibility that pre- and post-synaptic alpha-adrenergic receptors can be differentiated by a clinical pharmacological approach. We compared the ability of the alpha 1-selective antagonists, prazosin and urapidil, with the ability of the alpha 2-selective antagonist, yohimbine, to inhibit cardiovascular responses to the non-selective alpha-adrenergic agonist norepinephrine in 26 healthy volunteers. Urapidil (50 mg i.v.) and prazosin (5 mg orally) induced significant shifts to the right in the blood pressure dose-response curve of norepinephrine. Yohimbine (10 mg orally), on the other hand, increased norepinephrine sensitivity, as indicated by a significant shift to the left of the norepinephrine dose-response curve. In addition, urapidil and prazosin decreased norepinephrine potency on heart rate, whereas no effect on norepinephrine-induced heart rate elevation was observed with yohimbine. From the studies in which yohimbine was used it can be assumed that the post-synaptic response to norepinephrine is not counteracted by the drug-induced inhibition of sympathetic neurotransmitter release. Hence, our findings confirm the presence of pre- and post-synaptic alpha-adrenergic receptors in man.
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C015568:urapidil; D009638:Norepinephrine; D011224:Prazosin