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Eur J Pharmacol. 1998 May 22;349(2-3):199-203.

Induction of 5-hydroxytryptamine release by tramadol, fenfluramine and reserpine.

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GrĂ¼nenthal, Abteilung Pharmakologie, Aachen, Germany.


Tramadol is a centrally acting analgesic with several modes of action. Enhancement of 5-hydroxytryptamine release contributes to its actions. We investigated in which way tramadol induces 5-hydroxytryptamine release. Rat brain frontal cortex slices were preincubated with [3H]5-hydroxytryptamine, then superfused using conditions which impaired either carrier mediated release or exocytosis. Tramadol (10 and 100 microM), fenfluramine (1 microM) and reserpine (10 microM) enhanced the basal release of [3H]5-hydroxytryptamine. In the presence of a high concentration of 6-nitroquipazine effects of tramadol were reduced and those of fenfluramine abolished. Effects by reserpine were enhanced, indicating that [3H]5-hydroxytryptamine depletion was counteracted by reuptake. When NaCl was replaced by LiCl, tramadol did not affect [3H]5-hydroxytryptamine release, fenfluramine induced a small and reserpine a marked facilitation. Omission of CaCl2 did not alter fenfluramine and reserpine effects while those by tramadol were reduced. It is concluded that tramadol induces both carrier mediated 5-hydroxytryptamine release as well as exocytosis.

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