title: Anticonvulsant mechanisms of piperine, a piperidine alkaloid.
abstract: Piperine, a natural compound isolated from the fruits of Piper, is known to modulate several neurotransmitter systems such as serotonin, norepinephrine, and GABA, all of which have been linked to the development of convulsions. Fruits of Piper species have been suggested as means for managing seizure disorders. The present study was designed to elucidate the anticonvulsant effect of piperine and its mechanisms of action using in-silico, in-vivo and in-vitro techniques.PASS software was used to determine its possible activity and mechanisms. Furthermore the latency for development of convulsions and mortality rate was recorded in different experimental mouse models of epilepsy (pentylenetetrazole, maximal electroshock, NMDA, picrotoxin, bicuculline, BAYK-8644, strychnine-induced convulsions) after administration of various doses of piperine (5, 10 and 20 mg/kg, i.p.). Finally, the effect of piperine on Na(+) and Ca(2+) channels were evaluated using the whole cell patch clamp techniqueOur results revealed that piperine decreased mortality in the MES-induced seizure model. Moreover, piperine (10 mg/kg) delayed the onset of tonic clonic convulsions in the pentylenetetrazole test and reduced associated mortality. Furthermore, an anticonvulsant dose of piperine also delayed the onset of tonic clonic seizures in strychnine, picrotoxin and BAY K-8644. Complete protection against mortality was observed in BAYK-8644 induced convulsions. Finally, whole cell patch clamp analysis suggested an inhibitory effect of piperine on Na(+) channels. Together, our data suggest Na(+) channel antagonist activity as a contributor to the complex anticonvulsant mechanisms of piperine.
authors.affiliation: a Department of Pharmaceutical Sciences and Drug Research ; Punjabi University ; Patiala , Punjab , India.
authors.forename: Awanish
authors.initials: A
authors.lastname: Mishra
authors.affiliation: a Department of Pharmaceutical Sciences and Drug Research ; Punjabi University ; Patiala , Punjab , India.
authors.forename: Jasmine Kaur
authors.initials: JK
authors.lastname: Punia
authors.affiliation: b Department of Physiology & Pharmacology ; Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary ; Calgary , Alberta , Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Bladen
authors.affiliation: b Department of Physiology & Pharmacology ; Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary ; Calgary , Alberta , Canada.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Zamponi
authors.affiliation: a Department of Pharmaceutical Sciences and Drug Research ; Punjabi University ; Patiala , Punjab , India.
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Goel
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D052117:Benzodioxoles / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D051379:Mice; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D053284:Polyunsaturated Alkamides / Q000494:pharmacology* / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy*; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000470:Alkaloids; D000927:Anticonvulsants; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D026941:Sodium Channel Blockers; D012964:Sodium; D002118:Calcium; C008922:piperine
keywords: Chemoconvulsants; Na+ and Ca2+ channel; alkaloids; anticonvulsant activity; anticonvulsant mechanism; piperine