Anticonvulsant effects of agomelatine in mice.
Agomelatine is a potent MT1 and MT2 melatonin receptor agonist and a 5-HT2C serotonin receptor antagonist. We analyzed whether agomelatine has anticonvulsant properties. The anticonvulsant activity of agomelatine (25, 50 or 75 mg/kg, i.p.) was evaluated in mouse models of pentylenetetrazole (PTZ-85 mg/kg, i.p.), pilocarpine (400mg/kg, i.p.), picrotoxin (7 mg/kg, i.p.), strychnine (75 mg/kg, i.p.) or electroshock-induced convulsions. In the PTZ-induced seizure model, agomelatine (at 25 or 50mg/kg) showed a significant increase in latency to convulsion, and agomelatine (at 50 or 75 mg/kg) also increased significantly time until death. In the pilocarpine-induced seizure model, only agomelatine in high doses (75 mg/kg) showed a significant increase in latency to convulsions and in time until death. In the strychnine-, electroshock- and picrotoxin-induced seizure models, agomelatine caused no significant alterations in latency to convulsions and in time until death when compared to controls. Our results suggest that agomelatine has anticonvulsant activity shown in PTZ- or pilocarpine-induced seizure models.
School of Medicine, University of Fortaleza (UNIFOR)/RENORBIO, Rua Desembargador Floriano Benevides Magalhães, 221 3° Andar-60811-690, Fortaleza, Ceará, Brazil.
Carlos Clayton Torres
CC
Aguiar
Anália Barbosa
AB
Almeida
Paulo Victor Pontes
PV
Araújo
Germana Silva
GS
Vasconcelos
Edna Maria Camelo
EM
Chaves
Otoni Cardoso
OC
do Vale
Danielle Silveira
DS
Macêdo
Francisca Cléa Florenço
FC
de Sousa
Glauce Socorro de Barros
GS
Viana
Silvânia Maria Mendes
SM
Vasconcelos
D000081:Acetamides / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D005260:Female; D008550:Melatonin / Q000819:agonists*; D051379:Mice; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013997:Time Factors; D009281:Naphthalenes
D000081:Acetamides; D000927:Anticonvulsants; D003292:Convulsants; D008550:Melatonin; C084711:agomelatine; D009281:Naphthalenes