title: Involvement of ATP-sensitive potassium channels and the opioid system in the anticonvulsive effect of zolpidem in mice.
abstract: Zolpidem is a hypnotic medication that mainly exerts its function through activating γ-aminobutyric acid (GABA)A receptors. There is some evidence that zolpidem may have anticonvulsive effects. However, the mechanisms underlying this effect have not been elucidated yet. In the present study, we used the pentylentetrazole (PTZ)-induced generalized seizure model in mice to investigate whether zolpidem can affect seizure threshold. We also further evaluated the roles of ATP-sensitive potassium (KATP) channels as well as μ-opioid receptors in the effects of zolpidem on seizure threshold. Our data showed that zolpidem in a dose-dependent manner increased the PTZ-induced seizure threshold. The noneffective (i.e., did not significantly alter the PTZ-induced seizure threshold by itself) doses of KATP channel blocker (glibenclamide) and nonselective opioid receptor antagonist (naloxone) were able to inhibit the anticonvulsive effect of zolpidem. Additionally, noneffective doses of either KATP channel opener (cromakalim) or nonselective μ-opioid receptor agonist (morphine) in combination with a noneffective dose of zolpidem exerted a significant anticonvulsive effect on PTZ-induced seizures in mice. A combination of noneffective doses of naloxone and glibenclamide, which separately did not affect zolpidem effect on seizure threshold, inhibited the anticonvulsive effects of zolpidem. These results suggest a role for KATP channels and the opioid system, alone or in combination, in the anticonvulsive effects of zolpidem.
authors: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mehdi
authors: M
authors: Sheikhi
authors: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Armin
authors: A
authors: Shirzadian
authors: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Amir
authors: A
authors: Dehdashtian
authors: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Shayan
authors: S
authors: Amiri
authors: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Sattar
authors: S
authors: Ostadhadi
authors: Department of Neurology, University of Massachusetts School of Medicine, Worcester, MA 01655, USA. Electronic address: m82.ghasemi@gmail.com.
authors: Mehdi
authors: M
authors: Ghasemi
authors: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpour@yahoo.com.
authors: Ahmad Reza
authors: AR
authors: Dehpour
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D019806:Cromakalim / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D051379:Mice; D009020:Morphine / Q000627:therapeutic use; D010433:Pentylenetetrazole / Q000009:adverse effects; D011725:Pyridines / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
chemical_list: D000701:Analgesics, Opioid; D000927:Anticonvulsants; D054086:KATP Channels; D011725:Pyridines; D019806:Cromakalim; D005680:gamma-Aminobutyric Acid; D009020:Morphine; D000077334:Zolpidem; D010433:Pentylenetetrazole
keywords: K(ATP) channel; Mice; Morphine; Opioid; Pentylentetrazole; Seizure; Zolpidem