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.
Highlights
Metoclopramide is a benzamine derivative [1], used in humans and animals [2,3], as centrally acting antiemetic and reduces stomach movement
In second experiment we evaluated the peripheral and central antinociception effect for further examine the synergistic interaction between metoclopramide and xylazine given as combination, whereas significantly increased the latency time of thermal response and significant decreased in writhing number of acetic acids in compares with control groups (Table 2)
The present study revealed that the type of interaction of xylazine and metoclopramide as a combination was synergistic at fixed ration 0.5:0.5 of individual ED50 for each at the level of analgesia, we supported this finding by calculate the value of Y interaction index, which was lower than 1 [23,24,25], this finding similar to the previous studies of other combinations as ketamine with metoclopramide [3], xylazine with tramadol [15] and metoclopramide with diphenhydramine [30] in mice, as all of them was synergistic interaction at level of analgesia
Summary
Metoclopramide is a benzamine derivative [1], used in humans and animals [2,3], as centrally acting antiemetic and reduces stomach movement. These effects related to its centrally antagonizing of dopamine D2-receptors antagonist, and serotonergic effects 5HT3 [4]. Combination of xylazine with dipyrone [14] or tramadol [15] in mice and in chicks [16] or with chlorpromazine in sheep [17] and chicks [18], produced safe and effective analgesia at low doses of each drug (synergistic antinociceptive effect)
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