title: Effects of D-penicillamine on pentylenetetrazole-induced seizures in mice: involvement of nitric oxide/NMDA pathways.
abstract: Besides the clinical applications of penicillamine, some reports show that use of D-penicillamine (D-pen) has been associated with adverse effects such as seizures. So, the purpose of this study was to evaluate the effects of D-pen on pentylenetetrazole (PTZ)-induced seizures in male NMRI mice. It also examined whether N-methyl-D-aspartate (NMDA) receptor/nitrergic system blockage was able to alter the probable effects of D-pen. Different doses of D-pen (0.1, 0.5, 1, 10, 100, 150, and 250 mg/kg) were administered intraperitoneally (i.p.) 90 min prior to induction of seizures. D-Penicillamine at a low dose (0.5 mg/kg, i.p.) had anticonvulsant effects, whereas at a high dose (250 mg/kg, i.p.), it was proconvulsant. Both anti- and proconvulsant effects of D-pen were blocked by a single dose of a nonspecific inhibitor of nitric oxide synthase (NOS), L-NAME (10 mg/kg, i.p.), and a single dose of a specific inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitroindazole (30 mg/kg, i.p.). A selective inhibitor of iNOS, aminoguanidine (100 mg/kg, i.p.), had no effect on these activities. An NMDA receptor antagonist, MK-801 (0.05 mg/kg, i.p.), alters the anti- and proconvulsant effects of D-pen. The results of the present study showed that the nitric oxide system and NMDA receptors may contribute to the biphasic effects of D-pen, which remain to be clarified further.
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Rahimi
authors.affiliation: Neuroscience Research Center, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Mitra
authors.initials: M
authors.lastname: Sadeghzadeh
authors.affiliation: Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehrak
authors.initials: M
authors.lastname: Javadi-Paydar
authors.affiliation: Neuroscience Research Center, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran; Pharmaceutics, Neuroscience and Physiology Research Centers, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Heidary
authors.affiliation: Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Jazaeri
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpour@yahoo.com.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D003292:Convulsants / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010396:Penicillamine / Q000008:administration & dosage / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D009569:Nitric Oxide; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D010433:Pentylenetetrazole
keywords: Mice; Nitric oxide; Nitric oxide synthase inhibitors; Pentylenetetrazole; Seizure; d-Penicillamine