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

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 [H-3]5-hydroxytryptamine, then superfused using conditions which impaired either carrier mediated release or exocytosis. Tramadol (10 and 100 mu M), fenfluramine (1 mu M) and reserpine (10 mu M) enhanced the basal release of [H-3]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 [H-3]5-hydroxytryptamine depletion was counteracted by reuptake. When NaCl was replaced by LiCl, tramadol did not affect [H-3]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. (C) 1998 Elsevier Science B.V. All rights reserved.