title: Additive anticonvulsant effects of agmatine and lithium chloride on pentylenetetrazole-induced clonic seizure in mice: involvement of α₂-adrenoceptor.
abstract: After 60 years, lithium is still the mainstay in the treatment of mood disorders and widely used in clinic. In addition to its mood stabilizer effects, lithium also shows some anticonvulsant properties. Similar to lithium, agmatine also plays a protective role in the CNS against seizures and has been reported to enhance the effect of different antiepileptic agents. Moreover, both agmatine and lithium have modulatory effects on α(2)-adrenoceptors. So, we designed this study: 1) to investigate whether agmatine and lithium show an additive effect against clonic seizures induced by pentylenetetrazole; 2) to assess whether this additive effect is mediated through the α(2)-adrenoceptor or not. In our study, acute administration of a single effective dose of lithium chloride (30 mg/kg, i.p.) increased the seizure threshold. Pre-treatment with low and, per se, non-effective doses of agmatine (1 and 3mg/kg) potentiated a sub-effective dose of lithium (10mg/kg). Interestingly, the anticonvulsant effects of these effective combinations of lithium and agmatine were prevented by pre-treatment with low and non-effective doses of yohimbine [α(2)-adrenoceptor antagonist] (0.1 and 0.5mg/kg). On the other hand, clonidine [α(2)-adrenoceptor agonist] augmented the anticonvulsant effect of a sub-effective combination of lithium (5mg/kg i.p.) and agmatine (1mg/kg) at relatively low doses (0.1 and 0.25mg/kg). In summary, our findings demonstrate that agmatine and lithium chloride exhibit additive anticonvulsant properties which seem to be mediated through α(2)-adrenoceptor.
authors.affiliation: Tehran University of Medical Sciences, School of Medicine, Department of Pharmacology, Iran.
authors.forename: Arash
authors.initials: A
authors.lastname: Bahremand
authors.forename: Pouya
authors.initials: P
authors.lastname: Ziai
authors.forename: Borna
authors.initials: B
authors.lastname: Payandemehr
authors.forename: Reza
authors.initials: R
authors.lastname: Rahimian
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Amouzegar
authors.forename: Mina
authors.initials: M
authors.lastname: Khezrian
authors.forename: Laleh
authors.initials: L
authors.lastname: Montaser-Kouhsari
authors.forename: Maryam Aghaei
authors.initials: MA
authors.lastname: Meibodi
authors.forename: Ali
authors.initials: A
authors.lastname: Ebrahimi
authors.forename: Abbas
authors.initials: A
authors.lastname: Ghasemi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghasemi
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000376:Agmatine / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018021:Lithium Chloride / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D000376:Agmatine; D018021:Lithium Chloride; D010433:Pentylenetetrazole