Pharmacological evidence for the activation of Ca2+-activated K+ channels by meloxicam in the formalin test.
The possible participation of K+ channels in the antinociceptive action of meloxicam was assessed in the 1% formalin test. Local peripheral administration of meloxicam produced a dose-dependent antinociception only during the second phase of the formalin test. K+ channel blockers alone did not modify formalin-induced nociceptive behavior. However, local peripheral pretreatment of the paw with charybdotoxin and apamin (large- and small-conductance Ca2+-activated K+ channel inhibitors, respectively), 4-aminopyridine and tetraethylammonium (non-selective voltage-dependent K+ channel inhibitors), but not glibenclamide or tolbutamide (ATP-sensitive K+ channel inhibitors), dose-dependently prevented meloxicam-induced antinociception. It is concluded that meloxicam could open large- and small-conductance Ca2+-activated K+ channels, but not ATP-sensitive K+ channels, in order to produce its peripheral antinociceptive effect in the formalin test. The participation of voltage-dependent K+ channels was also suggested, but since non-selective inhibitors were used the data await further confirmation.
Area Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, Mexico. mario_i_ortix@hotmail.com
Mario I
MI
Ortiz
Gilberto
G
Castañeda-Hernández
Vinicio
V
Granados-Soto
D015761:4-Aminopyridine / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D018999:Charybdotoxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005557:Formaldehyde; D005905:Glyburide / Q000494:pharmacology; D000077239:Meloxicam; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying; D013843:Thiazines; D013844:Thiazoles; D018999:Charybdotoxin; D005557:Formaldehyde; D001030:Apamin; D019789:Tetraethylammonium; D014044:Tolbutamide; D015761:4-Aminopyridine; D005905:Glyburide; D000077239:Meloxicam