Depression is a mood disorder, which affects an estimated more then 100 million people worldwide. The treatment of depression has been revolutionized by the introduction of SSRIs that possess fewer side effects than tricyclic antidepressants. The major drawback with the current line of SSRIs is that they have a delayed onset before the beneficial therapeutic effect is observed.
One approach to create a fast-acting SSRI is to combine, in a single molecule, an agent with SSRI activity and 5-HT_1A antagonist activity [1-4].
The aim of this work was the design, synthesis and biological evaluation of new compounds with dual 5-HT_1A and 5-HT-T affinity.
The structure of new compounds was confirmed by ¹H and ¹³C NMR spectral data as well as by C, H, N analysis.
Target compounds were tested for their affinity for 5-HT_1A receptor and 5-HT reuptake inhibition using radioligand binding assay.
The tested compounds showed relatively high affinity for the 5-HT_1A receptor and serotonin reuptake inhibition at nanomolar concentration for dual activities
(K_i = 4,8 - 10,9 and K_i = 15,3 - 35,2 respectively).

R1 = H, CH3, OCH3, F R2 = H, CH3, OCH3, F R3 = H, OCH3R4 = H, CH3

[1] Blier P., Bergeron R.; J. Clin. Psychiat. 59, 16 (1998)
[2] Hjorth S.; J. Neurochem. 60, 776 (1993)
[3] Gartside S. E., Umbers V., Hajos M., Sharp T.; Br. J. Pharmacol. 115, 1064 (1995)
[4] Meagher K. L., Mewshaw R. E., Evrard D. A., Zhou P., Smith D. L., Scerni R., Spangler T., Abulhawa S., Shi X., Schechter L. E., Andree T. H.; Bioorg. Med. Lett. 11, 1885 (2001)

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