Differential effect of zileuton, a 5-lipoxygenase inhibitor, against nociceptive paradigms in mice and rats.
Pain is commonly associated with inflammation. Several mediators including prostaglandins have been implicated in pain and inflammation. However, the recent reports indicated the role of leukotrienes as signaling molecules in pain. The present study was aimed to evaluate the effect of 5-LOX inhibitor, zileuton in nociceptive paradigms including inflammatory pain. Acetic acid-induced writhing, tail flick and hot plate tests to assess pain response were used. The effect on carrageenan-induced mechanical hyperalgesia, and acetic acid-induced vascular permeability was also determined. Zileuton (ED50=31.81 mg/kg p.o.), zafirlukast (ED50=6.19 mg/kg p.o.), montelukast (ED50=7.17 mg/kg p.o.) inhibited acetic acid-induced writhing in mice. Further, zileuton and ZK 158252, leukotriene B4 receptor antagonist did not alter basal response against tail flick and hot plate assays. Acetic acid-induced vascular permeability was significantly inhibited by zileuton. Oral administration of zileuton showed efficacy against carrageenan-induced mechanical hyperalgesia and also reversed histological changes in paw biopsies. These data suggest that zileuton, a 5-LOX inhibitor, exhibited antinociceptive effect in paradigms of inflammatory pain.
Singh
Vijay Pal
VP
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.
Patil
Chandrashekhar S
CS
Kulkarni
Shrinivas K
SK
D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002351:Carrageenan; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D005260:Female; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000473:pathology; D007211:Indoles; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D020024:Leukotriene Antagonists / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D048448:Phenylcarbamates; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000494:pharmacology
D000085:Acetates; D000700:Analgesics; D003521:Cyclopropanes; D007211:Indoles; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; D048448:Phenylcarbamates; D011804:Quinolines; D018102:Receptors, Leukotriene B4; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds; D002351:Carrageenan; C093875:montelukast; D019342:Acetic Acid; C063449:zileuton; D006918:Hydroxyurea; C062735:zafirlukast