Antidepressant and antipsychotic activity of new quinoline- and isoquinoline-sulfonamide analogs of aripiprazole targeting serotonin 5-HT(1)A/5-HT(2)A/5-HT(7) and dopamine D(2)/D(3) receptors.

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Zajdel P, Marciniec K, Maslankiewicz A, Grychowska K, Satala G, Duszynska B, Lenda T, Siwek A, Nowak G, Partyka A, Wrobel D, Jastrzebska-Wiesek M, Bojarski AJ, Wesolowska A, Pawlowski M

Antidepressant and antipsychotic activity of new quinoline- and isoquinoline-sulfonamide analogs of aripiprazole targeting serotonin 5-HT(1)A/5-HT(2)A/5-HT(7) and dopamine D(2)/D(3) receptors.

Eur J Med Chem. 2013 Feb;60:42-50. doi: 10.1016/j.ejmech.2012.11.042. Epub 2012 Dec 5.

PubMed ID

23279866 [ View in PubMed

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Abstract

A series of new quinoline- and isoquinoline-sulfonamide analogs of aripiprazole was synthesized to explore the influence of two structural features - replacement of ether/amide moiety with sulfonamide one, and localization of a sulfonamide group in the azine moiety. In contrast to aripiprazole, compound 33 (N-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propyl)quinoline-7-sulfonamide) and 39 (N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)isoquinoline-3-sulfonamide) displaying multireceptor 5-HT(1A)/5-HT(2A)/5-HT(7)/D(2)/D(3) profile, and behaving as 5-HT(1A) agonists, D(2) partial agonists, and 5-HT(2A)/5-HT(7) antagonists, produced significant antidepressant activity in FST in mice. On the other hand, their 4-isoquinolinyl analog 40 (N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)isoquinoline-4-sulfonamide), with similar receptor binding and functional profile, additionally displayed remarkable antipsychotic properties in the MK-801-induced hyperlocomotor activity in mice.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Aripiprazole	5-hydroxytryptamine receptor 1A	Ki (nM)	5.6	N/A	N/A	Details
Aripiprazole	5-hydroxytryptamine receptor 2A	Ki (nM)	21	N/A	N/A	Details
Aripiprazole	5-hydroxytryptamine receptor 6	Ki (nM)	90	N/A	N/A	Details
Aripiprazole	5-hydroxytryptamine receptor 7	Ki (nM)	26	N/A	N/A	Details
Aripiprazole	Dopamine D2 receptor	Ki (nM)	0.8	N/A	N/A	Details
Aripiprazole	Dopamine D3 receptor	Ki (nM)	9.7	N/A	N/A	Details