Role of drugs affecting potassium channels on morphine analgesia in mice

ABSTRACT

The modification of antinociceptive effect of morphine by either K[+] channel blockers such as glibenclamide or K[+] channel openers such as diazoxide and minoxidil was evaluated. Antinociceptive activity of morphine was measured by tail-immersion test and hot plate test in mice. The intraperitoneal administration of morphine [5 mg/kg] elicited a time-dependent antinociceptive effect [after 15, 30, 60 and 120 minutes post injection]. The selective blockers of ATP -senstive K[+] channels glibenclamide [15mg, IP] antagonized the spinal [tail-immersion test] and supraspinal [hot plate lest] antinociception induced by 5 mg/kg morphine IP. In contrast the antinociceptive effect of morphine was enhanced by intraperitoneal administration of either diazoxide [140 mg/kg] or minoxidil [14 mg/kg] [K[+] channels openers] in a time dependent manner [after 15, 30, 60 and 120 minutes post injection]. These results suggested that K[+] channels openers as diazoxide and minoxidil potentiated the spinal and supraspinal analgesia induced by morphine. In addition the selective blockers of ATP -senstive K[+] channels glibenclamide antagonized the spinal and supraspinal analgesia induced by morphine in time dependent manners