Peripheral and spinal mechanisms of antinociceptive action of lumiracoxib.
The possible participation of the nitric oxide (NO)-cyclic GMP-K(+) channel pathway, serotonergic or opioidergic system on lumiracoxib-induced local or intrathecal antinociception was assessed in the formalin test. Local or intrathecal administration of lumiracoxib dose-dependently produced antinociception in the second phase of the test. Moreover, local or intrathecal pretreatment with N(G)-L-nitro-arginine methyl ester (L-NAME, NO synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, guanylyl cyclase inhibitor), glibenclamide (ATP-sensitive K(+) channel blocker), charybdotoxin and apamin (large- and small-conductance Ca(2+)-activated-K(+) channel blockers, respectively) or margatoxin (voltage-dependent K(+) channel blocker), but not N(G)-D-nitro-arginine methyl ester (D-NAME) or vehicle, significantly prevented lumiracoxib-induced antinociception. The intrathecal injection of methiothepin (serotonin receptor antagonist) reduced lumiracoxib-induced intrathecal antinociception. Local peripheral or intrathecal naloxone did not modify either local or intrathecal lumiracoxib-induced antinociception. Results suggest that lumiracoxib activates the NO-cyclic GMP-K(+) channels to produce local and intrathecal antinociception. Data also suggest that lumiracoxib activates the intrathecal serotonergic system, but not opioid receptors either at peripheral or spinal sites.
Lozano-Cuenca
Jair
J
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Calzada de los Tenorios 235, Colonia Granjas Coapa, Mexico.
Castañeda-Hernández
Gilberto
G
Granados-Soto
Vinicio
V
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D018999:Charybdotoxin / Q000008:administration & dosage / Q000494:pharmacology; D004008:Diclofenac / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005557:Formaldehyde; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008719:Methiothepin / Q000008:administration & dosage / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009498:Neurotoxins / Q000008:administration & dosage / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009930:Organic Chemicals / Q000008:administration & dosage / Q000494:pharmacology*; D010069:Oxadiazoles / Q000008:administration & dosage / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000700:Analgesics; D004791:Enzyme Inhibitors; D009498:Neurotoxins; D009930:Organic Chemicals; D010069:Oxadiazoles; D011810:Quinoxalines; D012604:Scorpion Venoms; D018999:Charybdotoxin; D004008:Diclofenac; D005557:Formaldehyde; D001030:Apamin; D009270:Naloxone; D008719:Methiothepin; C077910:margatoxin; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; C473384:lumiracoxib