*Correspondence: M. F. Guerrero. Pharmacy Department, School of Sciences, National University of Colombia. 14490 - Bogotá D.C. Colombia, AA. E-mail: mfguerrerop@unal.edu.co Article Brazilian Journal of Pharmaceutical Sciences vol. 50, n. 1, jan./mar., 2014 http://dx.doi.org/10.1590/S1984-82502011000100007 Anticonvulsant profile of 2-ethylthio-7-methyl-4-(4-methylphenyl) pyrazolo[1,5-a][1,3,5]triazine Martín Hermógenes Estrada 1 , Henry Insuasty 2 , Luis Enrique Cuca 3 , Mariel Marder 4 , Angélica Fierro 5 , Mario Francisco Guerrero 1,* 1 Pharmacy Department, School of Sciences, National University of Colombia, Bogotá, Colombia, 2 Chemistry Department, University of Nariño, Pasto, Colombia, 3 Chemistry Department, School of Sciences, National University of Colombia, Bogotá, Colombia, 4 Biochemistry and Pharmacy, IQUIFIB, Buenos Aires University, Buenos Aires, Argentina, 5 School of Chemistry and Biology, Santiago University of Chile, Santiago, Chile This work evaluates the central nervous effects in ICR strain mice of 2-ethylthio-7-methyl-4-(4- methylphenyl)pyrazolo[1,5-a][1,3,5]triazine (MH4b1), a compound obtained by an effcient one-step reaction of S,S-diethyl 4-methylbenzoylimidodithiocarbonate with 5-amino-3-methyl-1H-pyrazole, in order to assess its neuro-pharmacological profle. The tests applied were: maximal electroshock seizure (MES), pentylenetetrazole (PTZ) seizures, forced swimming, plus maze, marble burying, sleeping time, rota-rod and catalepsy. In addition, MH4b1 binding to the benzodiazepine site of the GABA-A receptor and MH4b1 inhibition of monoamine oxidase (MAO) subtypes A and B were evaluated. MH4b1 showed anticonvulsant effects in a dose dependent manner (30-300 mg/kg, p.o.) against MES and inhibition of MAO-B (IC 50 : 24.5 µM) without activity at the benzodiazepine site. These data suggest that MH4b1 has anticonvulsant properties related to MAO-B inhibition. Uniterms: Pyrazolo-triazine/anticonvulsant profle. Anticonvulsants/experimental study. Monoamine oxidase/inhibitors. Este trabalho avalia o efeito do 2-etiltio-7-metil-4-(4-metilfenil)pirazol[1,5-a][1,3,5]triazina (MH4b1) no sistema nervoso central de camundongos ICR. O MH4b1 foi obtido por a reação de 4-metilbenzoilimidoditiocarbonato de S,S-dietil e 5-amino-3-metil-1H-pirazol em uma única etapa. O perfl neurofarmacológico foi realizado por testes de convulsão induzida por eletrochoque (MES) e pentilenotetrazol (PTZ) e por testes de nado forçado, labirinto em cruz, esconder as esferas, sono barbitúrico, rota-rod e catalepsia. Também foi avaliada a união do MH4b1 ao o local de ligação de benzodiazepínicos do receptor GABA-A e a capacidade inibitória do MH4b1 sobre a monoaminoxidase (MAO) A e B. O MH4b1 mostrou efeito anticonvulsivante dependente da dose (30-300 mg) no teste do MES e apresentou atividade inibitória da MAO-B (CI 50 : 24.5 µM) sem interagir com o local de ligação de benzodiazepínicos do receptor. Os resultados sugerem que o MH4b1 tem atividade anticonvulsivante relacionada com a inibição da MAO-B. Unitermos: Pirazol-triazina/perfil anticonvulsivante. Anticonvulsivantes/estudo experimental. Monoaminoxidase/inibidores. INTRODUCTION The pyrazolo[1,5-a][1,3,5]triazine system has been a pharmacological structure for the development of drugs that are potentially useful for a wide range of disorders, including asthma (Junien et al., 1998), cancer (Nie et al., 2008; Popowycz et al., 2009), infammatory (el-Hawash et al., 1998), thrombogenic (Raboisson et al., 2002) and affective disorders such as major depression and pathological anxiety (Gilligan et al., 2009). An efficient method for the preparation of pyrazolo[1,5-a][1,3,5]triazines by the interaction of S,S-diethyl aroyliminodithiocarbonates with 5-amino-3-methylpyrazole to obtain novel 4-aryl- 2-ethylthio-7-methylpyrazolo[1,5- a][1,3,5]triazines