Complementary and synergistic antinociceptive interaction between the enantiomers of tramadol.

摘要: The explanation for the co-existence of opioid and nonopioid components tramadol-induced antinociception appears to be related different, but complementary interactive, pharmacologies its enantiomers. (+) enantiomer had Ki values only 1.33, 62.4 54.0 microM at mu, delta kappa receptors, respectively. (-) even lower affinity mu sites (Ki = 24.8, 213 53.5 microM, was most potent inhibitor serotonin uptake 0.53 microM) norepinephrine 0.43 microM). Basal release preferentially enhanced by stimulation-evoked enantiomer. enantiomers each independently produced centrally mediated in acetylcholine-induced abdominal constriction test (ED50 14.1 35.0 micrograms i.t., respectively). Racemic tramadol significantly more (P < .05) than theoretical additive effect (antinociceptive synergy). Synergy also demonstrated .1) mouse 55 degrees C hot-plate (i.p. route) rat Randall-Selitto yeast-induced inflammatory nociception model (i.v. i.p. routes). Critically, interacted less synergistically two side-effects inhibition colonic propulsive motility impairment rotarod performance. racemate were active a chronic (arthritic) pain model. Taken together, these findings provide rational coexistence dual might form basis understanding clinical profile.