Original Scientific Article Combining analgesic medications with distinct pharmacodynamics may result in effective analgesia and reduced adverse effects by lowering dosages of one or both medications. The objective was to investigate the nature of interactions of metoclopramide and metamizole by measuring the antinociceptive and neurobehavioral effects in mice. The drugs were administered intraperitoneally (ip) in mice. The antinociceptive effect was determined by the up-and-down method. Isobolographic analysis was performed by simultaneous injection of the two drugs at ED50 ratios of 1:1 and 0.5:0.5. The treated mice were also subjected to an open-field behavioral test as well as dorsal immobility and negative geotaxis behavioral paradigms. The ED50 of metoclopramide and metamizole were 33.71 and 43 mg/kg ip, respectively. Lower ED50 was established for metoclopramide and metamizole by 48.44% and 47.49%, respectively when given at a ratio of 0.5:0.5, and by 35.81% and 29.88%, respectively at a ratio of 1:1. The combined dose of metoclopramide and metamizole (8 and 10 mg/kg, ip, respectively) significantly decreased the open field-activity test in mice. This was observed by lower number of squares crossing compared to the control. Additionally, the drug combination resulted in a substantial increase in the duration of dorsal immobility response and delayed the negative geotaxis task when compared with the control group. The results indicated that the interaction between metoclopramide and metamizole in lower dose ratio with ED50 50:50, was synergistic in producing analgesia in mice with reduced risk for adverse reaction but with decreased behavioral and motor neuronal activity. https://macvetrev.mk/LoadArticlePdf/361 2024-10-15 159 166 https://doi.org/10.2478/macvetrev-2024-0027 metoclopramide metamizole antinociceptive effect neurobehavioral hot plate Zena Sattam Hamed zenasattam@uomosul.edu.iq false 1 Pharmacology and Toxicology Department, College of Pharmacy, University of Mosul, Iraq LEAD_AUTHOR Khalid Ahmed Shaban false 2 Physiology, Biochemistry and Pharmacology Department, College of Veterinary Medicine, University of Mosul, Iraq AUTHOR Ghada Abdul-Munem Faris false 3 Physiology, Biochemistry and Pharmacology Department, College of Veterinary Medicine, University of Mosul, Iraq AUTHOR Lee, A., Kuo, B. (2010). 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