Dopamine and Serotonine receptor antagonists. Synthesis of aminoalkyl cyclanones as atipic antipsycotic
Raviña, E.
Departamento de Química Orgánica. Laboratorio de Química Farmacéutica. Facultad de Farmacia. 15706 Santiago de Compostela. España
Ars Pharm.36;(3);337-376, (1995)
Key words: Antipsychotic, Dopamine, SerotonineAbstract
A series of 3-aminomethyil tetralones and 2-aminoethyl cycloalkanones carrying o-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 potencial antipsychotic agents in receptor binding assays for dopamine D1 and D2 receptors and 5-HT2A serotonin receptors and in funcional and behavioral screens. The ratios of pKi's for 5-HT2A/D2 receptors may be useful for rapid sceening of new compounds and its potential induction of extrapyramidal symptoms (ratio values > 1.12 are predictive of an atypical antipsychotic profile). With the exception of QF 0100B, QF 0102B and QF 0309B, the new molecules had a ratio value in the range 1.08-1.20, while haloperidol showed a ratio of 0.93.
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-3ethyl-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 D1, D2 and 5-HT2A receptors. Teir affinities for D2 and 5-HT2A receptors are lower than haloperidol and comparable to the molindone.
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