Synthesis and preliminary pharmacological investigations of 1-(1,2-dihydro-2-acenaphthylenyl)piperazine derivatives as potential atypical antipsychotic agents in mice

In research towards the development of new atypical antipsychotic agents, o ne strategy is that the dopaminergic system can be modulated through manipu lation of the serotonergic system. The synthesis and preliminary pharmacolo gical evaluation of a series of potential atypical antipsychotic agents bas ed on the structure of 1-(1,2-dihydro-2-acenaphthylenyl)piperazine (7) is d escribed. Compound 7e, 5-{2-[4-(1,2-dihydro-2-acenaphthylenyl)piperazinyl]e thyl}-2,2-dihydro-1H-indol-2-one, from this series showed significant affin ities at the 5-HT1A and 5-HT2A receptors and moderate affinity at the D-2 r eceptor. 7e exhibits a high reversal of catalepsy induced by haloperidol in dicating its atypical antipsychotic nature. (C) 1999 Elsevier Science S.A. All rights reserved.