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 [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.
Grünenthal, Abteilung Pharmakologie, Aachen, Germany.
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W
Reimann
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F
Schneider
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D005277:Fenfluramine / Q000494:pharmacology*; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D014147:Tramadol / Q000494:pharmacology*
D000701:Analgesics, Opioid; D005277:Fenfluramine; D012701:Serotonin; D014147:Tramadol; D012110:Reserpine