title: Enhancement of inhibitory neurotransmission and inhibition of excitatory mechanisms underlie the anticonvulsant effects of Mallotus oppositifolius.
abstract: BACKGROUND
  Mallotus oppositifolius is a shrub that is used traditionally to treat epilepsy, but its potential has not been scientifically validated.
  
  
  OBJECTIVE
  This study investigated the anticonvulsant properties and possible mechanism of action of the 70% v/v hydroalcoholic extract of the leaves of M. oppositifolius.
  
  
  METHODS
  Inprinting control region (ICR) mice (25-30 g) were pretreated with the M. oppositifolius leaf extract (10-100 mg/kg) before administering the respective convulsants (pentylenetetrazole [PTZ], picrotoxin [PTX], strychnine [STR], 4-aminopyridine [4-AP], and pilocarpine). The effect of the extract in maximal electroshock seizure (MES) model was investigated also.
  
  
  METHODS
  Data were presented as mean ± standard error of the mean and were analyzed with one-way analysis of variance (ANOVA) or two-way ANOVA where appropriate with Newman-Keuls or Bonferroni post hoc test respectively. P < 0.05 was considered significant.
  
  
  RESULTS
  In both PTX and PTZ test, extract delayed the onset of seizures and reduced the frequency and duration of seizures. In the STR-induced seizure test, the extract significantly delayed the onset of seizures and reduced the duration of seizures. The extract also delayed the onset of clonic and tonic seizures as well as increasing the survival of mice in the 4-AP-induced seizure test. It further reduced the duration of tonic limb extensions in the MES test. In the pilocarpine-induced status epilepticus, the extract significantly delayed the onset of clonic convulsions and reduced the frequency and duration of seizures. Moreover, the anticonvulsant effect of the extract was attenuated by flumazenil, a benzodiazepine/gamma-aminobutyric acid (GABA) receptor antagonist.
  
  
  CONCLUSIONS
  These findings show that the extract has anticonvulsant effect possible mediated by GABAergic, glycinergic neurotransmission, and potassium channel conductions. It may also be acting by antagonizing muscarinic receptor activation and N-Methyl-D-aspartate receptor activation.
authors.affiliation: Department of Pharmacology and Toxicology, University of Ghana School of Pharmacy, College of Health Sciences, University of Ghana, Accr, Ghana.
authors.forename: Kennedy Kwami Edem
authors.initials: KK
authors.lastname: Kukuia
authors.affiliation: Department of Biomedical and Forensic Sciences, School of Biological Science, University of Cape Coast, Cape Coast, Ghana.
authors.forename: Elvis Ofori
authors.initials: EO
authors.lastname: Ameyaw
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Eric
authors.initials: E
authors.lastname: Woode
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Priscilla Kolibea
authors.initials: PK
authors.lastname: Mante
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Donatus Wewura
authors.initials: DW
authors.lastname: Adongo
keywords: Benzodiazepine/gamma-aminobutyric acid type A receptor; Mallotus oppositifolius; flumazenil; pilocarpine; seizures