Tramadol hydrochloride is a centrally acting analgesic agent that interacts with opioid, adrenergic, and serotonin receptors.1–3 One of the metabolites of tramadol, O-desmethyl-tramadol, has an affinity for opioid receptors approximately 200 times as great as the affinity for the parent drug, and it has been postulated that this metabolite is important for analgesic effects of tramadol.4,5
Tramadol is efficacious and tolerated well in humans and is increasingly being used to treat pain in dogs and cats. However, to our knowledge, limited data are available on the analgesic efficacy of tramadol in cats. Investigators in 1 study6 reported that tramadol had little or no effect on thermal and mechanical thresholds in cats. However, only 1 dose (1 mg/kg) was used in that study. Moreover, tramadol was administered SC in that study,6 and tramadol currently is not available in an injectable form in the United States, which limits the clinical applicability of the findings. In particular, if O-demethyl-tramadol is responsible for part of the analgesic effects of tramadol, then it is possible that oral administration results in better analgesia than parenteral administration because the first-pass metabolism would be expected to result in faster production of the active metabolite. In another study,7 tramadol decreased the MAC of sevoflurane in cats. However, decreases in MAC (or a lack thereof) should not be taken as evidence for analgesic effect because some drugs that cause a decrease in the MAC of inhalation anesthetics do not appear to result in analgesia, and drugs that result in analgesia do not always cause a decrease in MAC.8–12 Moreover, in that study,7 time for equilibration between end-tidal and effect-site concentrations appears inadequate, which limits the interpretability of the reported decrease in MAC.
The purpose of the study reported here was to characterize the effects of oral administration of tramadol on the thermal threshold in cats and the dose-dependent nature of this effect and to examine the relationship between plasma tramadol and O-desmethyl-tramadol concentrations and antinociceptive effect. We hypothesized that oral administration of tramadol would increase the thermal threshold in a dose-dependent manner.
Concentration that induces 50% of the maximum effect
Minimum alveolar concentration
Central venous catheterization set, Arrow International, Reading, Pa.
Tramadol hydrochloride, Akyma Pharmaceutical, Glasgow, Ky.
Tramadol, Cerilliant, Round Rocks, Tex.
HPLC grade acetronitrile, Burdick and Jackson, Muskegon, Mich.
Cerilliant, Round Rock, Tex.
TSQ Quantum Ultra, ThermoFisher Scientific, San Jose, Calif.
1100 Series, Agilent Technologies, Palo Alto, Calif.
ACE 3 C18, Mac-Mod Analytical, Chadds Ford, Pa.
LCQuan Thermo, Fisher Scientific, San Jose, Calif.
WinNonLin Pro 5.2, Pharsight Corp, Moutain View, Calif.
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