British Journal of Anaesthesia, Vol 79, Issue 3 352-356, Copyright © 1997 by The Board of Management and Trustees of the British Journal of Anaesthesia
T. A. Bamigbade, C. Davidson, R. M. Langford and J. A. Stamford
Tramadol is an atypical centrally acting analgesic agent with relatively
weak opioid receptor affinity in comparison with its antinociceptive
efficacy. Evidence suggests that block of monoamine uptake may contribute
to its analgesic actions. Therefore, we have examined the actions of
(+/-)-tramadol, (+)-tramadol, (-)-tramadol and O-desmethyltramadol (M1
metabolite) on electrically evoked 5-HT efflux and uptake in the dorsal
raphe nucleus (DRN) brain slice, measured by fast cyclic voltammetry.
Racemic tramadol and its (+)-enantiomer (both 5 mumol litre-1)
significantly blocked DRN 5-HT uptake (both P < 0.05) and increased
stimulated 5-HT efflux (P < 0.01 (+/-)-tramadol; P < 0.05
(+)-tramadol). The (-)-enantiomer and metabolite, O-desmethyltramadol, were
inactive at the concentration tested (5 mumol litre-1). For both
(+/-)-tramadol and the (+)-enantiomer, the action on 5-HT efflux preceded
an effect on 5-HT uptake, suggesting that uptake block was not the cause of
the increased 5-HT efflux and that tramadol might therefore have a direct
5-HT releasing action. This activity, at clinically relevant
concentrations, may help to explain the antinociceptive efficacy of
tramadol despite weak mu opioid receptor affinity and adds to evidence that
tramadol exerts actions on central monoaminergic systems that may
contribute to its analgesic effect.
LABORATORY INVESTIGATIONS
Actions of tramadol, its enantiomers and principal metabolite, O- desmethyltramadol, on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus
Department of Anaesthesia, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE; Anaesthetics Unit (Neurotransmission Laboratory), Royal London Hospital, Whitechapel, London E1 1BB, UK
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Zeidan, R. Kassem, N. Nahleh, H. Maaliki, M. El-khatib, M. M.R.F. Struys, and A. Baraka Intraarticular Tramadol-Bupivacaine Combination Prolongs the Duration of Postoperative Analgesia After Outpatient Arthroscopic Knee Surgery Anesth. Analg., July 1, 2008; 107(1): 292 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. Gillman Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity Br. J. Anaesth., October 1, 2005; 95(4): 434 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hara, K. Minami, and T. Sata The Effects of Tramadol and Its Metabolite on Glycine, {gamma}-Aminobutyric AcidA, and N-Methyl-d-Aspartate Receptors Expressed in Xenopus Oocytes Anesth. Analg., May 1, 2005; 100(5): 1400 - 1405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Altunkaya, Y. Ozer, E. Kargi, I. Ozkocak, M. Hosnuter, C. B. Demirel, and O. Babuccu The Postoperative Analgesic Effect of Tramadol When Used as Subcutaneous Local Anesthetic Anesth. Analg., November 1, 2004; 99(5): 1461 - 1464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. O. Rojas-Corrales, E. Berrocoso, J. Gibert-Rahola, and J. A. Mico Antidepressant-Like Effect of tramadol and its Enantiomers in Reserpinized Mice: Comparativestudy with Desipramine, Fluvoxamine, Venlafaxine and Opiates J Psychopharmacol, September 1, 2004; 18(3): 404 - 411. [Abstract] [PDF]
|
|
|
|
 |
|
 V K Podichetty, D J Mazanec, and R S Biscup Chronic non-malignant musculoskeletal pain in older adults: clinical issues and opioid intervention Postgrad. Med. J., November 1, 2003; 79(937): 627 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Alhashemi and A. M. Kaki Effect of intrathecal tramadol administration on postoperative pain after transurethral resection of prostate Br. J. Anaesth., October 1, 2003; 91(4): 536 - 540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Webb, S. Leong, P. S. Myles, and S. J. Burn The Addition of a Tramadol Infusion to Morphine Patient-Controlled Analgesia After Abdominal Surgery: A Double-Blinded, Placebo-Controlled Randomized Trial Anesth. Analg., December 1, 2002; 95(6): 1713 - 1718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Hopwood, C. A. Owesson, L. F. Callado, D. P. McLaughlin, and J. A. Stamford Effects of chronic tramadol on pre- and post-synaptic measures of monoamine function J Psychopharmacol, May 1, 2001; 15(3): 147 - 153. [Abstract] [PDF]
|
|
|
|
 |
|
 M. J. Garrido, M. Valle, M. A. Campanero, R. Calvo, and I. F. Trocóniz Modeling of the In Vivo Antinociceptive Interaction between an Opioid Agonist, (+)-O-Desmethyltramadol, and a Monoamine Reuptake Inhibitor, (-)-O-Desmethyltramadol, in Rats J. Pharmacol. Exp. Ther., October 1, 2000; 295(1): 352 - 359. [Abstract] [Full Text]
|
|
|
|
|
|
M. Valle, M. J. Garrido, J. M. Pavón, R. Calvo, and I. F. Trocóniz Pharmacokinetic-Pharmacodynamic Modeling of the Antinociceptive Effects of Main Active Metabolites of Tramadol, (+)-O-Desmethyltramadol and (-)-O-Desmethyltramadol, in Rats J. Pharmacol. Exp. Ther., May 1, 2000; 293(2): 646 - 653. [Abstract] [Full Text]
|
|