The central action, particularly potential antidepressant activity of WEB 1881, a new nootropic drug related to piracetam, was investigated in rats and mice. WEB 1881 antagonizes the reserpine- and apomorphine-induced hypothermia, potentiates the behavioral effect of DOPA and dihydroxyphenylserine, as well as the TRH-induced hyperthermia. Piracetam was only effective in the reserpine and DOPA tests. WEB 1881 is inactive in immobility test of Porsolt et al. It enhances the hind limb flexor reflex of the spinal rat, this effect being antagonized by prazosin and cyproheptadine. It exerts no effect on head twitches induced by L-5-hydroxytryptophan. The studied compound increases the noradrenaline and dopamine and turnover in the forebrain and brain stem. WEB 1881 given repeatedly potentiates the clonidine-induced aggressiveness and has no effect on the locomotor hyperactivity induced by D-amphetamine. The results indicate that in a number of tests WEB 1881 acts like other antidepressant drugs (but in others not), moreover, they suggest that this action is--at least partly--mediated by the central noradrenaline system.
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