ATP-sensitive K+ channel openers inhibit morphine withdrawal.
We studied the effects of two different ATP-sensitive K+ channel openers on naloxone-precipitated withdrawal in morphine-dependent mice. The i.c.v. administration of cromakalim and diazoxide (both at 5-40 micrograms/mouse) dose-dependently inhibited several signs of morphine withdrawal (number of jumps and episodes of forepaw tremors, and body weight loss). At present it is impossible to specify the exact mechanism(s) involved in this effect. However, considering that morphine opens K+ channels in neurons, it is tempting to suggest that K+ channel openers can mimic the effects of morphine on neuronal K+ currents, and as a consequence can act as substitutes for this drug during morphine withdrawal.
Robles
L I
LI
Department of Pharmacology, Medical School, University of Granada, Spain.
Barrios
M
M
Baeyens
J M
JM
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D019806:Cromakalim; D003981:Diazoxide / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D009270:Naloxone; D009020:Morphine; D000255:Adenosine Triphosphate; D003981:Diazoxide