Possible involvement of the dopaminergic system in the mode of action of the potential antidepressant trazium esilate

Trazium esilate (EGYT-3615) is structurally an as-triazino isoquinolinium salt which showed considerable activity in pharmacological tests characteristic for antidepressants (antagonism of tetrabenazine, potentiation of yohimbine, behavioral despair). The compound exhibited minimal sedative effect. Some findings suggest that it influences the central dopaminergic system. The drug potentiated actions of amphetamine such as stereotypy and hypermotility. It differentially blocked the hypothermic and the stereotypy inducing action of apomorphine. Trazium esilate also inhibited the cataleptic state provoked by bulbocapnine in mice. In higher dose it decreased the plasma Prolactin level in rats. The compound potentiated the effect of norepinephrine on isolated vas deferens of the rat. Trazium esilate is a weak displacer on a1-, a2- and D2-receptors, however, it induced a2-receptor desenzitization after repeated treatment. It had no influence on rat brain cortical noradrenaline and striatal dopamine release evoked by high K+ concentration, but it increased the spontaneous dopamine outflow in rat striatum. The compound also elevated the striatal dopamine and DOPAC levels both after acute and chronic treatment.