Release studies with rat brain cortical synaptosomes indicate that tramadol is a 5-hydroxytryptamine uptake blocker and not a 5-hydroxytryptamine releaser.
Tramadol is a centrally acting opioid analgesic whose mechanism of action could also involve an increase in central serotoninergic transmission. Thus, tramadol inhibits synaptosomal serotonin (5-hydroxytryptamine, 5-HT) reuptake and induces tritium release from [3H]5-HT-preloaded slices. We investigated the effect of (+/-)-tramadol in release studies with superfused rat brain cortex synaptosomes preloaded with [3H]5-HT. Tramadol had no releasing effect up to 30 microM, whereas at 10 microM tramadol significantly inhibited by 45% D-fenfluramine-induced [3H]5-HT release. At 100 microM, tramadol showed a slight releasing effect in the absence or in the presence of pargyline, which was not augmented in synaptosomes pre-exposed to Ro 04-1284 (2-ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-2H-benzo [a]quinolizin-2-ol hydrochloride), a reserpine-like compound that enhances cytoplasmic 5-HT levels. In summary, (+/-)-tramadol behaved as a classical 5-HT uptake blocker (like citalopram) and not as a substrate of the 5-HT carrier with indirect 5-HT mimetic properties (like D-fenfluramine).
D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy- / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D005277:Fenfluramine / Q000494:pharmacology; D008297:Male; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014147:Tramadol / Q000494:pharmacology*