Anticonvulsive effects of intracerebroventricular administration of rutin in rats Marjan Nassiri-Asl a, ⁎ , Schwann Shariati-Rad b , Farzaneh Zamansoltani c a Department of Pharmacology, School of Medical Sciences, Qazvin University, Qazvin, Iran b School of Medical Sciences, Qazvin University of Medical Sciences, Qazvin, Iran c Department of Anatomy, School of Medical Sciences, Qazvin University, Qazvin, Iran Received 19 November 2007; received in revised form 14 January 2008; accepted 14 January 2008 Available online 19 January 2008 Abstract Various synthetic derivatives of natural flavonoids are known to have neuroactive properties. The aim of the present study was to investigate the anticonvulsant effects of rutin (3, 3′,4′, 5, 7-pentahydrohyflavone-3-rhamnoglucoside), a flavonoid which is an important dietary constituent of food and plant-based beverages. To this end, we assessed the anticonvulsant effects of rutin in rats treated with pentylenetetrazole (PTZ) (90 mg/kg, i.p.) and sought to clarify this mechanism. Intracerebroventricular (i.c.v.) injection of rutin dose-dependently affected minimal clonic seizures (MCS) and generalized tonic–clonic seizures (GTCS) induced by PTZ, through increments in seizure onset. Additionally, pretreatment with flumazenil (5 nM, i.c.v.) abolished the anticonvulsant effects of rutin during the onset of both seizures. These results indicate that rutin has anticonvulsant effects in the brain, possibly through positive allosteric modulation of the GABA A receptor complex via interaction at the benzodiazepine site. © 2008 Elsevier Inc. All rights reserved. Keywords: Anticonvulsant; Benzodiazepine; Flavonoids; GABA A receptor; Rutin 1. Introduction Epilepsy is a serious and common neurological condition. In contemporary society, the frequency and importance of epilepsy can hardly be overstated from epidemiologic studies. However, in most studies, the overall incidence of epilepsy in developed societies has been found to be around 50 cases per 100,000 persons per year, and rises steeply with age (Poole et al., 2000; Ropper and Brown, 2005). Seizures are controlled in nearly 70% of patients with epilepsy, mostly by pharmacologically modulating membrane ion channels or GABAergic or gluta- matergic transmission (Sander, 2003). γ-aminobutyric acid type A (GABA A ) receptors are targets for neuroactive drugs, such as benzodiazepines, and this interaction mediates their anxiolytic, hypnotic and anticonvul- sant effects at the benzodiazepine site on the receptors (Tsang and Xue, 2004). Classical benzodiazepines, the most widely prescribed drugs, exert their therapeutic effects by binding to the benzodiazepine site of GABA A receptors, and allosterically modulate chloride flux through the ion channel complex (Wang et al., 2005). They have multiple actions and a broad range of side effects (Medina et al., 1997; Wang et al., 2005). On the other hand, natural products from folk remedies have contributed significantly in the discovery of modern drugs and can be an alternative source for antiepileptic drugs with novel structures and better safety and efficacy profiles (Raza Available online at www.sciencedirect.com Progress in Neuro-Psychopharmacology & Biological Psychiatry 32 (2008) 989 – 993 www.elsevier.com/locate/pnpbp Abbreviations: ANOVA, analysis of variance; AP, anterior–posterior; CNS, central nervous system; DV, dorsal–ventral; DZ, diazepam; FMZ, flumazenil; GABA, γ-aminobutyric acid; GABA A, γ-aminobutyric acid type A; GABA-T, GABA transaminase; GTCS, generalized tonic–clonic seizures; i.c.v, intracer- ebroventricular; i.p, intraperitoneal; MCS, minimal clonic seizures; ML, medial–lateral; n, number of animals; PTZ, pentylenetetrazole; SSADH, succinic semialdehyde dehydrogenase. ⁎ Corresponding author. Department of Pharmacology, Qazvin University of Medical Sciences, Qazvin, P.O. Box: 341197-5981, Iran. Tel.: +98 2813336001; fax: +98 2813324970. E-mail address: marjannassiriaslm@gmail.com (M. Nassiri-Asl). 0278-5846/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2008.01.011