Interaction of morphine and potassium channel openers on experimental models of pain in mice.
Combination of opioid and potassium channel openers holds immense potential for the treatment for most acute and chronic pain. Therefore, the study was performed to assess the interaction between morphine and K(+) -channel openers. Swiss albino mice of either sex weighing between 25 and 30 g were used for the study. The study assesses the interaction between morphine and K(+) -channel openers (cromakalim, diazoxide and minoxidil), when administered intraperitoneally, using formalin and tail-flick tests in mice. Both morphine and K(+) -channel openers produced significant antinociception at higher doses in both the behavioral tests. Lower doses of morphine and K(+) -channel openers had no significant effect on tail-flick latency, while the same drugs had significant antinociceptive effect on formalin test. The combination of lower doses of morphine and K(+) -openers was observed to have significant antinociceptive effect in both the behavioral tests. Administration of naloxone prior to morphine or K(+) -channel openers antagonized the analgesic effect of morphine but not of K(+) -channel openers, whereas prior administration of glibenclamide antagonized the effect of both morphine and K(+) -channel openers. The study, therefore, suggests that the common site of action of morphine and K(+) -channel openers is at the levels of K(+) -channels rather than at the level of receptors. However, such interaction depends on the differential sensitivity to different pain stimulus.
Khanna
Naresh
N
Department of Pharmacology, University College of Medical Sciences, University of Delhi, Delhi 110095, India. naresh.khanna@gmail.com
Malhotra
Rachpal S
RS
Mehta
Ashish K
AK
Garg
Gobind R
GR
Halder
Sumita
S
Sharma
Krishna K
KK
D000818:Animals; D002120:Calcium Channel Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D019806:Cromakalim / Q000008:administration & dosage / Q000627:therapeutic use; D003981:Diazoxide / Q000008:administration & dosage / Q000627:therapeutic use; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008914:Minoxidil / Q000008:administration & dosage / Q000627:therapeutic use; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods; D015221:Potassium Channels / Q000187:drug effects
D002120:Calcium Channel Agonists; D015221:Potassium Channels; D019806:Cromakalim; D009270:Naloxone; D008914:Minoxidil; D009020:Morphine; D003981:Diazoxide; D005905:Glyburide