| 17825569 |
Paluchowska MH, Bugno R, Duszynska B, Tatarczynska E, Nikiforuk A, Lenda T, Chojnacka-Wojcik E: The influence of modifications in imide fragment structure on 5-HT (1A) and 5-HT (7) receptor affinity and in vivo pharmacological properties of some new 1-(m-trifluoromethylphenyl) piperazines. Bioorg Med Chem. 2007 Nov 15;15(22):7116-25. Epub 2007 Aug 22.
New, flexible (7, 9, 11 and 13) and rigid (8, 10, 12 and 14) imides with a 1-(m-trifluorophenyl) piperazine fragment and a tetramethylene or a 1e,4e-cyclohexylene spacer, respectively, showed very high affinity (K (i)=0.3-34 nM) and agonistic in vivo activity for 5-HT (1A) receptors. Flexible new compounds and the previously described 5 also bound to 5-HT (7) receptors (K (i)=21-134 nM). Selected glutarimide derivatives, that is, the most potent postsynaptic 5-HT (1A) receptor agonist rigid compound 8 and its flexible analogue 7, as well as the previously described full agonist-rigid compound 6 and the partial agonist-its flexible counterpart 5 exhibited moderate affinity for alpha (1)-adrenoceptors (K (i)=85 - 268 nM), but were practically devoid of any affinity for dopamine D (2) sites. Those glutarimides demonstrated anxiolytic- (5 and 7) and antidepressant-like (5, 6 and 8) activity in the four-plate and the swim tests in mice, respectively; at the same time, however, they inhibited the locomotor activity of mice. The antidepressant-like effect of 8 was significantly stronger than that induced by imipramine used as a reference antidepressant. |
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