Possible involvement of potassium channels in peripheral antinociception induced by metamizol: lack of participation of ATP-sensitive K+ channels.
The present work assessed the possible participation of K+ channels in the peripheral antinociceptive action of metamizol in the 1% formalin test. Ipsilateral, but not contralateral, local peripheral administration of metamizol 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 Ca(2+)-activated K+ channel blockers, respectively), 4-aminopyridine and tetraethylammonium (voltage-dependent K+ channel inhibitors), but not glibenclamide or tolbutamide (ATP-sensitive K+ channel inhibitors), dose-dependently prevented metamizol-induced antinociception. The above results suggest that metamizol could open large- and small-conductance Ca(2+)-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 nonselective inhibitors were used, the data await further confirmation.
Ortiz
Mario I
MI
Sección Externa de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico, D.F., Mexico.
Castañeda-Hernández
Gilberto
G
Granados-Soto
Vinicio
V
D015761:4-Aminopyridine / Q000494:pharmacology; D018528:ATP-Binding Cassette Transporters; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001030:Apamin / Q000494:pharmacology; D019540:Area Under Curve; D018999:Charybdotoxin / Q000494:pharmacology; D004177:Dipyrone / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005557:Formaldehyde; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels; D010147:Pain Measurement / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D000894:Anti-Inflammatory Agents, Non-Steroidal; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D018999:Charybdotoxin; D005557:Formaldehyde; D001030:Apamin; D004177:Dipyrone; D019789:Tetraethylammonium; D014044:Tolbutamide; D015761:4-Aminopyridine; D005905:Glyburide