A Study Investigating the Synergistic Analgesic Effects of Nefopam and Medetomidine in a Multimodal Pain Management Approach in Mice | ||
| Journal of Applied Veterinary Sciences | ||
| Article 12, Volume 10, Issue 3, July 2025, Pages 129-136 PDF (376.11 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/javs.2025.389940.1628 | ||
| Authors | ||
| Hazem Ahmed Khalil; Gada Abdul Al-munem Faris* | ||
| Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq | ||
| Abstract | ||
| This study explored the type of analgesic interaction between nefopam and medetomidine and evaluated their safety profiles in a mouse model as no previous studies had examined their pharmacological interaction at the antinociceptive level. Adult male and female mice (n=6-7 per group) were administered ascending/descending doses of nefopam or medetomidine alone or in a combination via intraperitoneal injection. Analgesic efficacy was determined using the hot plate test (55°°C) and writhing reflex technique. The ED50 values were calculated via the up-and-down method, isobolographic analysis assessed drug interaction types and LD50 values were derived to assess acute toxicity. Nefopam alone exhibited an ED50 of 5.66 mg/kg intraperitoneal (I.P.), while medetomidine showed an ED50 of 93.05 mg/kg I.P. Combined administration of nefopam with a fixed medetomidine dose (0.65 mg/kg) reduced the ED50 of nefopam by 44%. At the double ED50 dosage for each drug, concurrent intraperitoneal injection of the two drugs completely inhibits the writhing reflex (100%) elicited by acetic acid compared with each drug alone and with the control group. Isobolographic analysis confirmed synergetic interaction between two drugs at 1:1 and 0.5:0.5 of ED50 ratios, with interaction indices (y) of 0.92 and 0.58, respectively. The LD50 values were 78.46 mg/kg (nefopam) and 1230.75 µg/kg (medetomidine), yielding therapeutic indices (LD50/ED50) of 14 and 13, indicative of wide safety margins. These findings demonstrate a potent synergistic analgesic effect between nefopam and medetomidine, allowing for significant dose reductions without losing efficacy. This combination’s favorable safety profile supports its clinical potential as a non-opioid alternative for acute pain management. | ||
| Keywords | ||
| Isobolographic analysis; Medetomidine; Mice model; Nefopam; Synergistic analgesic | ||
| References | ||
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