Dopamine and Serotonine receptor antagonists. Synthesis of aminoalkyl cyc1anones as atipic antipsycotic.
Abstract
A series of 3-aminomethyl tetralones and 2-aminoethyl cycloalkanones carrying 0-
methoxy phenylpiperazine, p-fluoro butyrophenone and p-fluor benzoyl piperidine fragments
have been prepared by original synthetic procedures. The new compounds obtained have
been evaluated as potential antipsychotic agents in receptor binding assays for dopamine
DI and D2 receptors and 5-HT2A serotonin receptors and in funcional and behavioral
screens. The ratios of pKi's for 5-HTJ D2 receptors may be useful for rapid screening
of new compounds and its potential induction of extrapyramidal symptoms (ratio
values > l.12 are predictive of an atypical antipsychotic profile). With the exception of
In the catalepsy test (predictive test for induction of extrapyramidal symptoms) the
values obtained were in accordance with a atypical antipsychotic drugs profile.
Likewise, a few 2-methyl-3-ethyl-5-aminomethyl-4-oxo-4, 5, 6, 7-tetrahydro indols
(QF 0400B, QF 0402B, QF 0403B, QF 0404B) analogous of neuroleptic molindone
have been also prepared and evaluated in receptor binding assays for Di' D2 and 5-HT2A
receptors. Their affinities for D2 and 5-HT 2A receptors are lower than haloperidol and
comparable to the molindone.
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