title: Monoterpenoid terpinen-4-ol exhibits anticonvulsant activity in behavioural and electrophysiological studies.
abstract: Terpinen-4-ol (4TRP) is a monoterpenoid alcoholic component of essential oils obtained from several aromatic plants. We investigated the psychopharmacological and electrophysiological activities of 4TRP in male Swiss mice and Wistar rats. 4TRP was administered intraperitoneally (i.p.) at doses of 25 to 200 mg/kg and intracerebroventricularly (i.c.v.) at concentrations of 10, 20, and 40 ng/2 μL. For in vitro experiments, 4TRP concentrations were 0.1 mM and 1.0 mM. 4TRP (i.p.) inhibited pentylenetetrazol- (PTZ-) induced seizures, indicating anticonvulsant effects. Electroencephalographic recordings showed that 4TRP (i.c.v.) protected against PTZ-induced seizures, corroborating the behavioural results. To determine whether 4TRP exerts anticonvulsant effects via regulation of GABAergic neurotransmission, we measured convulsions induced by 3-mercapto-propionic acid (3-MP). The obtained results showed involvement of the GABAergic system in the anticonvulsant action exerted by 4TRP, but flumazenil, a selective antagonist of the benzodiazepine site of the GABAA receptor, did not reverse the anticonvulsant effect, demonstrating that 4TRP does not bind to the benzodiazepine-binding site. Furthermore, 4TRP decreased the sodium current through voltage-dependent sodium channels, and thus its anticonvulsant effect may be related to changes in neuronal excitability because of modulation of these channels.
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Rede Nordeste de Biotecnologia (RENORBIO), Caixa Postal 5009, 58051-900 João Pessoa, PB, Brazil ; Unidade Acadêmica de Tecnologia do Desenvolvimento, Centro de Desenvolvimento Sustentável do Semiárido, Universidade Federal de Campina Grande, 58540-000 Sumé, PB, Brazil.
authors.forename: Franklin F F
authors.initials: FF
authors.lastname: Nóbrega
authors.affiliation: Laboratório de Psicofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba, Caixa Postal 5009, 58051-900 João Pessoa, PB, Brazil.
authors.forename: Mirian G S S
authors.initials: MG
authors.lastname: Salvadori
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors.forename: Cintia J
authors.initials: CJ
authors.lastname: Masson
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Mello
authors.affiliation: Laboratório de Eletrofisiologia, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Campus do Itaperi, 60740-000 Fortaleza, CE, Brazil.
authors.forename: Tiago S
authors.initials: TS
authors.lastname: Nascimento
authors.affiliation: Laboratório de Eletrofisiologia, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Campus do Itaperi, 60740-000 Fortaleza, CE, Brazil.
authors.forename: José H
authors.initials: JH
authors.lastname: Leal-Cardoso
authors.affiliation: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal da Paraíba, 58051-900 João Pessoa, PB, Brazil.
authors.forename: Damião P
authors.initials: DP
authors.lastname: de Sousa
authors.affiliation: Laboratório de Psicofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba, Caixa Postal 5009, 58051-900 João Pessoa, PB, Brazil ; Departamento de Fisiologia e Patologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba, 58051-900 João Pessoa, PB, Brazil.
authors.forename: Reinaldo N
authors.initials: RN
authors.lastname: Almeida
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism; D057967:Infusions, Intraventricular; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010433:Pentylenetetrazole / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D058787:GABA-A Receptor Antagonists; D039821:Monoterpenes; D011963:Receptors, GABA-A; D013729:Terpenes; D005442:Flumazenil; C034019:terpinenol-4; D010433:Pentylenetetrazole