Synergistic interaction between meloxicam and aminoguanidine in formalin-induced nociception in mice.
OBJECTIVE
The objective of this study was to examine the nature of interaction between cyclooxygenase-2 inhibitor meloxicam and inducible nitric oxide synthase inhibitor aminoguanidine in formalin-induced nociception in mice and the possible therapeutic advantage.


METHODS
Antinociceptive effect of meloxicam (1, 3, 10 and 30 mg/kg, oral) and aminoguanidine (10, 30, 100 and 300 mg/kg, oral) and their combinations was examined in formalin-induced paw licking model in mice. Analysis of variance and isobolographic method were employed to identify the nature of antinociceptive interaction.


RESULTS
Higher doses of meloxicam (10 and 30 mg/kg) and aminoguanidine (100 and 300 mg/kg) produced significant reduction in paw licking time (antinociceptive) in late phase of formalin-induced nociception. Combination of sub-threshold dose of meloxicam (3 mg/kg) with increasing doses of aminoguanidine (10, 30, 100 and 300 mg/kg) resulted in synergistic antinociceptive effect. Similarly, co-administration of sub-threshold dose of aminoguanidine (30 mg/kg) with increasing doses of meloxicam (1, 3, 10 and 30 mg/kg) produced significant reduction in formalin-induced paw licking behaviour. The experimental ED(50) for combination with their confidence limits are below the confidence interval of theoretical line of additive interaction, suggesting synergistic nature of interaction between meloxicam and aminoguanidine in isobolographic analysis.


CONCLUSIONS
Co-administration of meloxicam and aminoguanidine showed synergistic antinociceptive effect which might possibly reduce gastrointestinal toxicity associated with the use of meloxicam.
Dudhgaonkar
Shailesh P
SP
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Uttar Pradesh, India.
Tandan
Surendra K
SK
Kumar
Dinesh
D
Arunadevi
R
R
Prakash
V Ravi
VR
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005557:Formaldehyde / Q000633:toxicity*; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D000077239:Meloxicam; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D010147:Pain Measurement; D013843:Thiazines / Q000008:administration & dosage / Q000627:therapeutic use*; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D006146:Guanidines; D013843:Thiazines; D013844:Thiazoles; D005557:Formaldehyde; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C004479:pimagedine; D000077239:Meloxicam