(+)-O-Desmethyltramadol and
(-)-O-Desmethyltramadol, in Rats
by
Valle M, Garrido MJ, Pavon JM, Calvo R, Troconiz IF
Department of Pharmacology,
School of Medicine,
University of Basque Country, Leioa,
Bizkaia, Spain.
J Pharmacol Exp Ther 2000 May 1; 293(2):646-653

ABSTRACT

TThe pharmacokinetics and pharmacodynamics of the two main metabolites of tramadol, (+)-O-desmethyltramadol and (-)-O-desmethyltramadol, were studied in rats. Pharmacodynamic endpoints evaluated were respiratory depression, measured as the change in arterial blood pCO(2), pO(2), and pH levels; and antinociception, measured by the tail-flick technique. The administration of 10 mg/kg (+)-O-desmethyltramadol in a 10-min i.v. infusion significantly altered pCO(2), pO(2), and pH values in comparison with baseline and lower-dose groups (P <.05). However, 2 mg/kg administered in a 10-min i.v. infusion was enough to achieve 100% antinociception without respiratory depression. Moreover, the beta-funaltrexamine pretreatment completely eliminated the antinociception of the 2-mg/kg dose, suggesting that such an effect is due to mu-opioid receptor activation. To describe and adequately characterize the in vivo antinociceptive effect of the drug, (+)-O-desmethyltramadol was given at different infusion rates of varying lengths (10-300 min). Pharmacokinetics was best described by a two-compartmental model. The time course of response was described using an effect compartment associated with a linear pharmacodynamic model. The estimates of the slope of the effect versus concentration relationship were significantly decreased (P <.05) as the length of infusion was increased, suggesting the development of tolerance. Doses of up to 8 mg/kg (-)-O-desmethyltramadol given in 10-min i.v. infusion did not elicit either antinociception in the tail-flick test or respiratory effects. These in vivo results are in accordance with the opiate and nonopiate properties reported for these compounds in several in vitro studies.

Dosage
Allodynia
Synthesis
Vanilloid-1
Immune response
Tramadol (Ultram)
Tramadol: seizures
Tramadol: dependence
Tramadol and analgesia
Tramadol: pharmacology
Tramadol and acute pain
Tramadol versus morphine
Tramadol versus oxycodone
Tramadol versus venlafaxine
Tramadol as an antidepressant
Tramadol versus buprenorphine
Tramadol and perioperative pain
Tramadol/sustained release preparation
Tramadol, depression and Parkinson's disease
CYP2D6 polymorphism and tramadol (Ultram) metabolism

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