title: A synergistic interaction between magnesium sulphate and ketamine on the inhibition of acute nociception in rats.
abstract: OBJECTIVE
  Magnesium is an endogenous voltage-dependent NMDA receptor-channel blocker and ketamine is a non-competitive NMDA receptor antagonist. Magnesium may potentiate the effect of ketamine in analgesia and anaesthesia, but may also interact in an opposing manner. This study aimed at evaluating type of the interaction between magnesium sulphate and ketamine administered systemically in rats with an acute nociceptive pain (tail-immersion test).
  
  
  METHODS
  Analgesic activity was assessed by tail-immersion test in male Wistar rats (200-250 g). The distal 5 cm of the tail was immersed in a warm water bath (55 ± 0.5°C) and the time for tail-withdrawal was measured as response latency.
  
  
  RESULTS
  Magnesium sulphate (2.5-30 mg/kg, s.c.) and ketamine (2.5-30 mg/kg, i.p.) administered alone did not produce any effect. However, significant antinociception (synergistic interaction) was revealed at the following doses of ketamine: magnesium sulphate of 5:5 mg/kg, 2.5:5 mg/kg and 10:5 mg/kg. The effect was not dose-dependent, and a greater response was obtained when ketamine was administered before magnesium sulphate.
  
  
  CONCLUSIONS
  This study revealed that (1) magnesium sulphate and ketamine given alone were not effective against acute nociceptive pain in rats, but (2) a combination of both drugs resulted in synergistically inhibited nociception, (3) which occurred only at selected low doses and proportions of the medications in a combination and (4) suggested the importance of the order of drug administration.
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. katarinasavicvujovic@gmail.com.
authors.forename: K R
authors.initials: KR
authors.lastname: Savic Vujovic
authors.forename: S
authors.initials: S
authors.lastname: Vuckovic
authors.forename: D
authors.initials: D
authors.lastname: Srebro
authors.forename: B
authors.initials: B
authors.lastname: Medic
authors.forename: R
authors.initials: R
authors.lastname: Stojanovic
authors.forename: C
authors.initials: C
authors.lastname: Vucetic
authors.forename: M
authors.initials: M
authors.lastname: Prostran
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007649:Ketamine / Q000008:administration & dosage*; D008278:Magnesium Sulfate / Q000008:administration & dosage*; D008297:Male; D059225:Nociception / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy / Q000473:pathology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D000700:Analgesics; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D008278:Magnesium Sulfate