Anticonvulsant profile of 2-ethylthio-7-methyl-4-(4-methylphenyl)pyrazolo[1, 5-a][1, 3, 5]triazine

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 efficient one-step reaction of S,S-diethyl 4-methylbenzoylimidodithiocarbonate with 5-amino-3-methyl-1H-pyrazole, in order to assess its neuro-pharmacological profile. 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 (IC50: 24.5 µM) without activity at the benzodiazepine site. These data suggest that MH4b1 has anticonvulsant properties related to MAO-B inhibition.

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 perfil 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 (CI50: 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.

Behavioural and neuroendocrine effects of aqueous extract of Boerhaavia diffusa Linn. in mice using tail suspension and forced swim tests – A preliminary study.

The present study was done to evaluate the effect of aqueous extract of B. diffusa on depression in mice using behavioral models such as tail suspension test (TST) and forced swim test (FST). The extract (50, 100 and 200 mg/kg, po) was administered for 14 successive days to Swiss young albino mice. On 14th day, 60 min after administration, mice were subjected to TST and FST. The administration of aqueous extract of B. diffusa (50, 100 and 200 mg/kg, po) significantly decreased immobility period in both TST and FST, indicating significant antidepressant-like activity. The lowest dose (50 mg/kg) of the extract decreased the immobility period most significantly in FST, showing most potent antidepressant-like action. The efficacy of the extract (50 mg/kg) was comparable to fluoxetine (20 mg/kg). The extract did not show any significant effect on locomotor activity. The extract showed significant monoamine oxidase -A inhibitory activity. There was no significant effect of the extract on plasma corticosterone levels. Prazosin (α1-adrenoceptor antagonist), sulpiride (selective D2-receptor antagonist), baclofen (GABAB agonist), and p-CPA (tryptophan hydroxylase inhibitor) significantly attenuated the extract-induced antidepressant-like effect, when tested in TST. The extract might produce antidepressant-like effect by interaction with α1-adrenoceptors, dopamine-D2 receptors, serotonergic, and GABAB receptors. Thus, aqueous extract of B. diffusa showed significant antidepressant-like activity in mice probably through involvement of monoaminergic and GABAergic systems.