Effect of cocaine on xylazine analgesic activity

The effect of cocaine on the antinociceptive action of xylazine (XLZ) was studied by the method of abdominal contortions in mice. While XLZ alone (0.5 mg/kg, sc) inhibited the contortions by 43%, cocaine (5 mg/kg, sc) produced 39% inhibition and combination of the two drugs reduced the contortions by 77%. Cocaine acted synergistically with XLZ, decreasing the ED50 from 0.42 to 0.13 mg/kg. The mechanism involved does not seem to be directly mediated by activation of alpha-2 receptors since pretreatment of the animals with yohimbine did not significantly influence the XLZ effect.