Evaluation of the antinociceptive effect of xylazine and it’s interaction with metoclopramide in the acute pain model in mice

Abstract

The study was designed to qualitative and quantitative evaluation of the antinociceptive effect of metoclopramide and xylazine each alone or as a concomitant administration in mice. Adult albino Swiss mice weighing 20-30 mg used in all experiments. By using the hot plate test, the individual analgesic dose (ED50) of metoclopramide and xylazine detected depending on the up and down method. Isobolographic analysis used to evaluate the type of interaction between two drugs at the ratio 0.5:0.5 of individual ED50 for each drug at the level of antinociception effect. Simultaneously administration of the double dose of individual ED50 and low doses (sedative, non-analgesic doses) of both drugs, also evaluated at the level of central and visceral analgesia using a hot plate and writhing response test respectively. The individual ED50 of xylazine and metoclopramide was 10.8 and 25.6mg/kg IP respectively. A synergistic interaction at the level of analgesia explored between two drugs at ratio 0.5:0.5 which represented as decreased in ED50 of metoclopramide and xylazine by 58.75 and 58.15% respectively. The animal suffered from only slight sedation and docile. Simultaneously IP administration of xylazine and metoclopramide at double dose of ED50 for each drug-induced significant increase in latency time of thermal response, as well as a significant decrease in writhes number, which induced by acetic acid in comparison with control groups. The percentage of analgesia at sub analgesic doses of a concomitant administration of both drugs was 100% in comparison with each drug alone. These results suggested safe and good use of both drugs in veterinary medicine.

Keywords

• xylazine
• metoclopramide
• analgesia
• hot plate
• acetic acid