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Pharmacology & toxicology

Hypotensive activity of the pineal indoleamine hormones melatonin, 5-methoxytryptophol and 5-methoxytryptamine.


PMID 10752670

Abstract

Injection of the pineal indoles melatonin, 5-methoxytryptophol and 5-methoxytryptamine via the external jugular vein elicited a dose-dependent depression in mean arterial pressure. Melatonin and 5-methoxytryptophol were approximately equipotent and a dose of 150 micromol/kg brought about a reduction of about 40 mmHg in mean arterial pressure. Methoxytryptamine exerted a much more potent hypotensive action. An abrupt decrement in mean arterial pressure by 30 mmHg occurred when the dose was only 2 nmol/kg. Subsequent increases in the dose further lowered the mean arterial pressure, but more gently. The other pineal indoles tested including 5-methoxyindoleacetic acid and 5-hydroxyindoleacetic acid, as well as 6-methoxy-2-benzoxazolinone, did not affect the mean arterial pressure when tested up to 80 micromol/kg. Methylene blue, a guanylate cyclase inhibitor, was not able to antagonize the hypotensive activity of melatonin, suggesting that the mechanism of action of melatonin does not involve guanylate cyclase. Lidocaine, which blocks sodium channels in perivascular nerves, antagonized the hypotensive action of melatonin.

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