2. Academic Validation
  3. Effects of D-penicillamine on pentylenetetrazole-induced seizures in mice: involvement of nitric oxide/NMDA pathways

Effects of D-penicillamine on pentylenetetrazole-induced seizures in mice: involvement of nitric oxide/NMDA pathways

  • Epilepsy Behav. 2014 Oct;39:42-7. doi: 10.1016/j.yebeh.2014.07.013.
Nastaran Rahimi 1,  Mitra Sadeghzadeh 2,  Mehrak Javadi-Paydar 3,  Mahmoud Reza Heidary 4,  Farahnaz Jazaeri 3,  Ahmad R Dehpour 5
Affiliations

Affiliations

  • 1 Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran.
  • 2 Neuroscience Research Center, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
  • 3 Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran.
  • 4 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.
  • 5 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.
PMID: 25173990 DOI: 10.1016/j.yebeh.2014.07.013
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.

Keywords

Mice; Nitric oxide; Nitric oxide synthase inhibitors; Pentylenetetrazole; Seizure; d-Penicillamine.

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