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Role of ATP-sensitive potassium channels in the biphasic effects of morphine on pentylenetetrazole-induced seizure threshold in mice. 2007

Hamed Shafaroodi, and Shahrzad Asadi, and Hamed Sadeghipour, and Mehdi Ghasemi, and Farzad Ebrahimi, and Sina Tavakoli, and Amir Reza Hajrasouliha, and Ahmad Reza Dehpour
Department of Pharmacology, Tehran Medical Unit, Islamic Azad University, Tehran, Iran.

Although several studies have indicated that the opioid receptor agonist morphine exerts biphasic effects on clonic seizure threshold, as yet little is known of the underlying mechanisms in this effect. In the present study, using the specific ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide and the specific K(ATP) channel opener cromakalim, the possible involvement of K(ATP) channels in the effects of morphine on pentylenetetrazole (PTZ)-induced seizure threshold in mice was investigated. Acute administration of lower doses of morphine (1, 3 and 7.5 mg/kg, i.p.) increased and higher doses of morphine (30 and 60 mg/kg, i.p.) decreased the PTZ-induced seizure threshold. Glibenclamide (2.5-5 mg/kg) increased the PTZ-induced seizure threshold. Non-effective dose of cromakalim (0.1 microg/kg) inhibited anticonvulsant effect of glibenclamide (5 mg/kg). Acute administration of non-effective dose of glibenclamide (1 mg/kg) interestingly inhibited both anticonvulsant and pro-convulsant effects of morphine and this effect was significantly reversed by cromakalim (0.1 microg/kg). These results support the involvement of K(ATP) channels in the modulation of seizure threshold by morphine.

UI MeSH Term Description Entries
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D008297 Male Males
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009294 Narcotics Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS. Analgesics, Narcotic,Narcotic Analgesics,Narcotic,Narcotic Effect,Narcotic Effects,Effect, Narcotic,Effects, Narcotic
D010433 Pentylenetetrazole A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility. Leptazole,Pentamethylenetetrazole,Pentetrazole,Cardiazol,Corasol,Corazol,Corazole,Korazol,Korazole,Metrazol,Metrazole,Pentazol,Pentylenetetrazol
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005905 Glyburide An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide Glibenclamide,Daonil,Diabeta,Euglucon 5,Euglucon N,Glybenclamide,HB-419,HB-420,Maninil,Micronase,Neogluconin,HB 419,HB 420,HB419,HB420

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