Tramadol inhibits norepinephrine transporter function at desipramine-binding sites in cultured bovine adrenal medullary cells

Anesthesia and Analgesia
Kenichiro SagataAkio Shigematsu

Abstract

Tramadol is a widely used analgesic, but its mode of action is not well understood. To study the effects of tramadol on norepinephrine transporter (NET) function, we assayed the effect of tramadol on [3H]-norepinephrine ([3H]-NE) uptake and [3H]-desipramine binding to plasma membranes isolated from bovine adrenal medulla. We then characterized [14C]-tramadol binding in cultured bovine adrenal medullary cells. Tramadol inhibited the desipramine-sensitive uptake of [3H]-NE by the cells in a concentration-dependent manner (50% inhibitory concentration = 21.5 +/- 6.0 microM). Saturation analysis revealed that tramadol increased the apparent Michaelis constant of [3H]-NE uptake without changing the maximal velocity, indicating that inhibition occurred via competition for the NET (inhibition constant, K(i) = 13.7 microM). Tramadol inhibited the specific binding of [3H]-desipramine to plasma membranes. Scatchard analysis of [3H]-desipramine binding revealed that tramadol increased the apparent dissociation constant (K(d)) for binding without altering maximal binding, indicating competitive inhibition (K(i) = 11.2 microM). The binding of [14C]-tramadol to the cells was specific and saturable, with a K(d) of 18.1 +/- 2.4 microM. These f...Continue Reading

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Citations

Mar 24, 2007·Journal of Pharmacological Sciences·Kouichiro MinamiYoichi Ueta
Jun 1, 2006·Expert Review of Pharmacoeconomics & Outcomes Research·Christopher J EvansKim Le
Nov 15, 2014·Journal of Anesthesia·Kouichiro MinamiYasuhito Uezono
Apr 19, 2016·Behavioural Pharmacology·Majid Jafari-SabetAli Dizaji-Ghadim
Jun 16, 2004·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Kouichiro MinamiAkio Shigematsu
Feb 26, 2013·Autonomic & Autacoid Pharmacology·N H ShahJ Peedicayil
Dec 3, 2014·Journal of the American Veterinary Medical Association·Cherlene DelgadoLesley J Smith
Jun 27, 2014·Journal of Feline Medicine and Surgery·Yenny Indrawirawan, Trudi McAlees
Sep 19, 2017·Expert Opinion on Drug Discovery·Lidia BravoEsther Berrocoso
Jan 12, 2019·The American Journal of Drug and Alcohol Abuse·Mitra-Sadat Sadat-ShiraziMohammad-Reza Zarrindast
Mar 1, 2012·Autonomic & Autacoid Pharmacology·A KumarK Ernest
Oct 8, 2014·Anesthesiology and Pain Medicine·Fatemeh ZeraatiMohammad Hadi Farjoo
Oct 29, 2004·Clinical Pharmacokinetics·Stefan Grond, Armin Sablotzki
Apr 26, 2015·Clinical Pharmacokinetics·Dorte LassenKim Brøsen
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Jun 23, 2009·Veterinary Anaesthesia and Analgesia·Mohammad Reza SeddighiThomas J Doherty

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