Antidepressant- and anxiolytic-like activity of 7-phenylpiperazinylalkyl-1-3-dimethyl-purine-2-6-dione derivatives with diversified 5-HT?A receptor functional profile

Authors
Anna Partyka, Gra?yna Ch?o?-Rzepa, Anna Wasik, Magdalena Jastrz?bska-Wi?sek, Adam Bucki, Marcin Ko?aczkowski, Grzegorz Sata?a, Andrzej J Bojarski, Anna Weso?owska


Lab
Department of Clinical Pharmacy, Jagiellonian University Medical College, Kraków, Poland

Journal
Bioorg. Med. Chem.

Abstract
Continuing our earlier study in a group of purine-2,6-dione derivatives of long chain arylpiperazines (LCAPs), a series of 8-unsubstituted 7-phenylpiperazin-4-yl-alkyl (4-14) and 7-tetrahydroisoquinolinyl-alkyl (15-17) analogues were synthesized and their serotonin 5-HT1A, 5-HT2A, 5-HT6, 5-HT7 and dopamine D2 receptor affinities were determined. The study allowed us to identify some potent 5-HT1A receptor ligands with additional moderate affinity for 5-HT2A, 5-HT7 and dopamine D2 receptors. Compounds 9, 12, 13 and 14, with the highest 5HT1A receptor affinity, were selected for further functional in vivo studies and behavioural evaluation of antidepressant- and antianxiety-like activity. Compounds 9, 12 and 13 showed features of agonists of pre- and/or post-synaptic 5-HT1A receptors, whereas 14 was classified as an antagonist of postsynaptic sites. Moreover, derivatives 9 and 14 acted as antagonists of 5-HT2A receptors. In behavioural studies, compounds 9 and 13 showed antidepressant-like activity in the mouse forced swim test, and their effects were similar or stronger than those of imipramine. Compounds 9, 12 and 14 displayed potential anxiolytic-like properties in the mouse four-plate test, similar or even greater than those of the reference anxiolytic drug, diazepam.

BIOSEB Instruments Used
Aron Test or Four Plates Test (LE830)

Source :

http://www.pubfacts.com/detail/25435254/Antidepressant--and-anxiolytic-like-activity-of-7-phenylpiperazinylalkyl-13-dimethyl-purine-26-dione

Publication request

Thank you for your interest in our product range and your request for this publication, which will be sent to you if the research team and the journal allow it. Our commercial team will contact you as soon as possible.