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Journal of Pharmacology And Experimental Therapeutics, Vol. 155, Issue 2, 288-295, 1967
Copyright © 1967 by American Society for Pharmacology and Experimental Therapeutics

EFFECTS OF HYDROXYAMPHETAMINE (PAREDRINE) ON THE FUNCTION OF THE SYMPATHETIC NERVOUS SYSTEM IN NORMOTENSIVE SUBJECTS

John R. Gill Jr. 1, Dean T. Mason 1, and Frederic C. Bartter 1

1 Clinical Endocrinology Branch and the Cardiology Branch, National Heart Institute, National Institutes of Health, Bethesda, Maryland

Hydroxyamphetamine (Paredrine) was given for 10 to 12 days to seven normotensive women, at a maximal dosage of 400 mg/ day. Supine mean arterial blood pressure (97 ± 4 (S.E.M.) mm Hg) was unchanged, but significant postural hypotension appeared (standing mean arterial pressure, 89 ± 4 mm Hg, P < .01). The mean post-Valsalva overshoot in systolic arterial preecure was significantly reduced from 31.3 ± 7 to 20.3 ± 8.8 mm Hg (P < .05) by hydroxyamphetamine. The increase in forearm vascular resistance which occurs reflexly on cold stimulation was also significantly reduced by hydroxyamphetamine. These effects of prolonged treatment with hydroxyamphetamine suggest that it impairs function of the sympathetic nervous system. As free and conjugated urinary norepinephrine were not significantly changed by hydroxyamphetamine, it probably does not produce blockade by impairing synthesis of norepinephrime. Hydroxyamphetamine not only discharges norepinephrine from tissues but also leads to the accumulation in tissues of the beta-hydroxylated metabolite, agr-methyloctopamine. The latter compound, which has a weak pressor action as compared to that of norepinephrine, is released by nerve stimulation and could impair normal neurotransmission either by being a neurotransmitter less effective than norepinephrine or by interfering with the action of norepinephrine at its effector sites, or by both mechanisms.

Submitted on June 17, 1966
Accepted on August 4, 1966




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