The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Jan 1992
Comparative StudyOpioid and nonopioid components independently contribute to the mechanism of action of tramadol, an 'atypical' opioid analgesic.
Tramadol hydrochloride produced dose-related antinociception in mouse abdominal constriction [ED50 = 1.9 (1.2-2.6) mg/kg i.p.], hot-plate [48 degrees C, ED50 = 21.4 (18.4-25.3) mg/kg s.c.; 55 degrees C, ED50 = 33.1 (28.2-39.1) mg/kg s.c.] and tail-flick [ED50 = 22.8 (19.2-30.1) mg/kg s.c.] tests. Tramadol also displayed antinociceptive activity in the rat air-induced abdominal constriction [ED50 = 1.7 (0.7-3.2) mg/kg p.o.] and hot-plate [51 degrees C, ED50 = 19.5 (10.3-27.5) mg/kg i.p.] tests. The antinociceptive activity of tramadol in the mouse tail-flick test was completely antagonized by naloxone, suggesting an opioid mechanism of action. ⋯ The possibility that this additional activity contributes to the antinociceptive activity of tramadol was supported by the finding that systemically administered yohimbine or ritanserin blocked the antinociception produced by intrathecal administration of tramadol, but not morphine, in the rat tail-flick test. These results suggest that tramadol-induced antinociception is mediated by opioid (mu) and nonopioid (inhibition of monoamine uptake) mechanisms. This hypothesis is consistent with the clinical experience of a wide separation between analgesia and typical opioid side effects.