Release studies with rat brain cortical synaptosomes indicate that tramadol is a 5-hydroxytryptamine uptake blocker and not a 5-hydroxytryptamine releaser

Marco Gobbi, Tiziana Mennini

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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 μM, whereas at 10 μM tramadol significantly inhibited by 45% d-fenfluramine-induced [3H]5-HT release. At 100 μM, 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). Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)23-26
Number of pages4
JournalEuropean Journal of Pharmacology
Volume370
Issue number1
DOIs
Publication statusPublished - Apr 1 1999

Fingerprint

Tramadol
Synaptosomes
Serotonin
Brain
Fenfluramine
2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-2H-benzo(a)quinolizin-2-ol
Pargyline
Citalopram
Tritium
Reserpine
Opioid Analgesics

Keywords

  • (±)-Tramadol
  • 5-HT (5-hydroxytryptamine, serotonin) carrier
  • 5-HT (5-hydroxytryptamine, serotonin) release
  • Synaptosome

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

@article{72cd57ad8c624442a63645bc011c26da,
title = "Release studies with rat brain cortical synaptosomes indicate that tramadol is a 5-hydroxytryptamine uptake blocker and not a 5-hydroxytryptamine releaser",
abstract = "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 μM, whereas at 10 μM tramadol significantly inhibited by 45{\%} d-fenfluramine-induced [3H]5-HT release. At 100 μM, 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). Copyright (C) 1999 Elsevier Science B.V.",
keywords = "(±)-Tramadol, 5-HT (5-hydroxytryptamine, serotonin) carrier, 5-HT (5-hydroxytryptamine, serotonin) release, Synaptosome",
author = "Marco Gobbi and Tiziana Mennini",
year = "1999",
month = "4",
day = "1",
doi = "10.1016/S0014-2999(99)00123-5",
language = "English",
volume = "370",
pages = "23--26",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Release studies with rat brain cortical synaptosomes indicate that tramadol is a 5-hydroxytryptamine uptake blocker and not a 5-hydroxytryptamine releaser

AU - Gobbi, Marco

AU - Mennini, Tiziana

PY - 1999/4/1

Y1 - 1999/4/1

N2 - 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 μM, whereas at 10 μM tramadol significantly inhibited by 45% d-fenfluramine-induced [3H]5-HT release. At 100 μM, 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). Copyright (C) 1999 Elsevier Science B.V.

AB - 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 μM, whereas at 10 μM tramadol significantly inhibited by 45% d-fenfluramine-induced [3H]5-HT release. At 100 μM, 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). Copyright (C) 1999 Elsevier Science B.V.

KW - (±)-Tramadol

KW - 5-HT (5-hydroxytryptamine, serotonin) carrier

KW - 5-HT (5-hydroxytryptamine, serotonin) release

KW - Synaptosome

UR - http://www.scopus.com/inward/record.url?scp=0032898039&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032898039&partnerID=8YFLogxK

U2 - 10.1016/S0014-2999(99)00123-5

DO - 10.1016/S0014-2999(99)00123-5

M3 - Article

C2 - 10323276

AN - SCOPUS:0032898039

VL - 370

SP - 23

EP - 26

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1

ER -