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Journal of Pharmacology And Experimental Therapeutics, Vol. 138, Issue 2, 170-180, 1962
Copyright © 1962 by American Society for Pharmacology and Experimental Therapeutics

MODIFICATION BY RESERPINE OF THE ACTION OF SYMPATHOMIMETIC AMINES IN SPINAL CATS; A CLASSIFICATION OF SYMPATHOMIMETIC AMINES

U. Trendelenburg 1, A. Muskus 1, W. W. Fleming 1, and B. Gomez Alonso de la Sierra 1

1 Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The modification by pretreatment with reserpine (one or two intraperitoneal injections of 3 mg/kg each 24, or 48 and 24 hours, prior to the experiment) of the dose-response curves of 14 sympathomimetic amines was studied in spinal cats; recorded were the responses of the nictitating membrane, the blood pressure and the heart rate.

Pretreatment of short duration with reserpine (previously found not to cause supersensitivity to norepinephrme) was found to distinguish three classes of sympathomimetic amines. (a) Norepinephrine-like amines were as potent in reserpine-pretreated as in normal preparations and may therefore be regarded as predominantly direct acting. (b) Tyramine-like amines were less effective after pretreatment with reserpine; the maxima of their dose-response curves were depressed, and this reduction of their maximal response was correlated with the reduction of the response of the nictitating membrane to nerve stimulation. Therefore they may be regarded as predominantly indirect acting. (c) Pretreatment with reserpine shifted the dose-response curves of several amines to the right without affecting their maxima (ephedrine, m-tyramine, etc.). These amines have both direct and indirect actions, and they seem to represent a gradual transition from the first to the second group rather than a distinct third group.

Five pairs of meta-OH and para-OH analogs were studied; all five meta-OH compounds had more pronounced direct effects than the para-OH analogs. It is concluded that the position of the phenolic hydroxyl group is of greater and the presence or absence of the alcoholic hydroxyl group in the beta-position of less importance than hitherto assumed.

Submitted on May 14, 1962




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