Alaproclate, a new selective 5-HT uptake inhibitor with therapeutic potential in depression and senile dementia

Publisher Website
Google Scholar
Abstract
Alaproclate, a new specific 5-HT uptake inhibitor, was examined for its action on several receptors in the brain, for its action on the NA, DA and 5-HT uptake mechanismsin vivo and for its action on brain biogenic amine content. Alaproclate was practically devoid of action on a number of receptors as examined in binding studiesin vitro: 5-HT, histamine-H1,α 1,-α 2-adrenergic and dopamine D2 receptors. Alaproclate had also a weak affinity for3H-norzimeldine binding sites in contrast to imipramine. Unlike the tricyclic antidepressants alaproclate had a negligible action on muscarinic receptors and failed to block muscarinic induced stimulationin vivo. Contrary to clomipramine alaproclate failed to block NA uptakein vivo. Alaproclate was found to display a regional selectivity in blocking 5-HT uptakein vivo (measured with the H 75/12-method). The compound was most potent in the hippocampus and hypothalamus followed by striatum and cerebral cortex with a low potency in the spinal cord. The results are discussed in relation to a previously presented carrier site model for serotonin reuptake.