Vuckovic, Sonja (7003869333)Sonja (7003869333)VuckovicSrebro, Dragana (55601466500)Dragana (55601466500)SrebroVujovic, Katarina Savic (56362541300)Katarina Savic (56362541300)VujovicProstran, Milica (7004009031)Milica (7004009031)Prostran2025-06-122025-06-122015https://doi.org/10.3109/13880209.2014.996821https://www.scopus.com/inward/record.uri?eid=2-s2.0-84945955125&doi=10.3109%2f13880209.2014.996821&partnerID=40&md5=3a6cdea9b9f495afaaf63e343aa3b933https://remedy.med.bg.ac.rs/handle/123456789/8374Context: Magnesium and MK-801 (dizocilpine), antagonists of N-methyl-D-aspartate receptors, are involved in the processing of pain. Objective: This study determines whether magnesium sulfate (MS) and MK-801 affects visceral inflammatory pain and determines a possible mechanism of action. Materials and methods: Analgesic activity was assessed using the acetic acid-induced writhing test in rats. MS (1-45 mg/kg) or MK-801 (0.005-0.03 mg/kg) was administrated subcutaneously (s.c.). To assess possible mechanisms of action, we examined the effects of L-NAME (10 mg/kg, intraperitoneal), methylene blue (0.5 mg/kg, s.c.), and glibenclamide (3 mg/kg, s.c.) on the effect of MS or MK-801. Results: MS and MK-801 showed biphasic and linear dose-response pattern, respectively. MS reduces the number of writhing on the dose of 1, 5, and 15 mg/kg by 60, 50, and 78%, respectively, while it has no effects on the doses of 30 and 45 mg/kg. MK-801 (0.005- 0.03 mg/kg) showed decrease in the number of writhing by 33-79%. The mean effective doses of MS and MK-801 were 6.6 (first phase) and 0.009 mg/kg, respectively. Both drugs did not impair the rotarod performance. L-NAME, methylene blue, and glybenclamide reduced the effect of MK-801 by 100, 43, and 64%, respectively, but not the effect of MS. Conclusions: The results suggest that MS and MK-801 may be useful analgesics in the management of visceral inflammatory pain, at doses that do not induce motor impairment. The modulation of NO/cGMP/K+ATP pathway plays an important role in the antinociceptive mechanism of MK-801, but does not contribute to the antinociceptive effect of MS. © 2015 Informa Healthcare USA, Inc.Acetic acid-induced writhingNitric oxideNMDA antagonistRotarod