Effects of 6-(o-chlorophenyl)-8-ethyl-1-methyl-4H-s-triazolo [3,4-c]thieno[2,3-e][1,4]diazepine (Y-7131) on the metabolism of biogenic amines in brain.

A new derivative of thienodiazepine, 6-(o-chlorophenyl)-8-ethyl-1-methyl-4H-s-triazolo[3,4-c]thieno[2,3-e][1,4]diazepine (Y-7131) decreased the turnover of 5-hydroxytryptamine (5-HT) but not that of dopamine (DA) in the rat brain. The potency of Y-7131 in inhibiting the 5-HT turnover was stronger than that of diazepam. Imipramine decreased the turnover of 5-HT, whereas chlorpromazine increased the turnover of DA. Y-7131 decreased the turnover of norepinephrine (NE) in the mouse brain. With diazepam, such an action was not recognized. Imipramine did not affect the turnover of NE, whereas chlorpromazine increased it. Y-7131 inhibited the uptake of NE in the mouse brain, although it did not inhibit the uptake of 5-HT. Diazepam was devoid of such an action. Imipramine inhibited the uptake of both amines. The increase of the turnover of 5-HT, NE and DA due to foot-shock stress in the rat brain was suppressed by the administration of Y-7131. In this antagonistic effect, Y-7131 was more potent than diazepam. Neither imipramine nor chlorpromazine showed these antagonistic effects. The results obtained suggest that Y-7131 has biochemical profiles similar to diazepam but differs from it in exhibiting inhibitory effect on the NE turnover and its uptake.