Anticonvulsant Properties of Some Newer Monoamine Oxidase Inhibitors

Abstract

Facilitation of experimental convulsions by reserpine (1) which persisted for several days was found to correspond with depletion of brain amines including 5-hydroxytryp tamine, adrenaline and noradrenaline. Decrease in the concentration of these amines was found to be responsible for such experimental convulsions. It has also been reported that inhibitors of the enzyme monoamine oxidase, responsible for the metabolism of bio genic amines, have pronounced anticonvulsant effect (2) presumably due to an increase in the concentration of brain amines. In the present study some quinazolone hydrazides (3) and quinazolone hydrazines (4) synthesized in this laboratory as monoamine oxidase inhibitors were tested for their ability to protect against convulsions produced in rats by subcutaneous injections of pentylenetetrazol. Attempts were made to investigate if the enzyme inhibition is related to anticonvulsant effects elicited by such 2,3-disubstituted quinazolones which have been shown to possess pronounced hypnotic (5) and anticon vulsant properties (6). METHODSThe synthesis of newer 2,3-disubstituted quinazolones and their in vitro effect on the monoamine oxidase activity of isolated rat liver mitochondria using tyramine as substrate have been reported elsewhere (3,4). In the present study in vivo inhibition of monoamine oxidase by quinazolone hydrazides and quinazolone hydrazines was determined by DOPA (3,4-dihydroxyphenylalanine) response test (7) and reserpine reversal test (8). DOPA response testAlbino mice of either sex weighing between 15-20 g were used. The mice were divided in groups of five and kept in separate cages. A group of 5 mice was used for each dose of these agents. Aqueous solution of DL-DOPA was prepared by first dissolving the powder in 1 N HCl and then adjusting the pH with dilute sodium hydroxide to as close to neutral as possible (6.0) avoiding any precipitate. All injections were made within 1 hour after the preparation of the solution (7). Quinazolone hydrazides and

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

“…MAO inhibition has been described as a possible anticonvulsant mechanism of action of some agents. In addition, MAO inhibition is also implied in sedative properties (Kohli et al, 1967). This fact is in accordance with the increase in the sleeping period obtained with MH4b1 in pentobarbitone tests in mice.…”

Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

“…MAO-A preferentially oxidizes NA and 5-HT and is selectively inhibited by clorgyline, while MAO-B preferentially deaminates β-phenylethylamine and is irreversibly inhibited by l -deprenyl (Ramsay, 2013). MAO activity has been shown to be linked to epilepsy since the 1960s (Plotnikoff et al, 1963; Kohli et al, 1967). For instance, MAO-B activity is elevated in hypometabolic regions of PWE with TLE due to activated astrocytes and gliosis (Kumlien et al, 1992), the most common histopathological abnormality seen in this focal epilepsy (Blümcke et al, 2013).…”