Munusamy, V. and Yap, B.K. and Buckle, M.J.C. and Doughty, S.W. and Chung, L.Y. (2013) Structure-based identification of aporphines with selective 5-HT2A receptor-binding activity. Chemical Biology & Drug Design, 81 (2). pp. 250-256. ISSN 1747-0277, DOI https://doi.org/10.1111/cbdd.12069.
Full text not available from this repository.Abstract
Selective blockade of the serotonin 5-HT2A receptor is a useful therapeutic approach for a number of disorders, including schizophrenia, insomnia and ischaemic heart disease. A series of aporphines were docked into a homology model of the rat 5-HT2A receptor using AutoDock. Selected compounds with high in silico binding affinities were screened in vitro using radioligand-binding assays against rat serotonin (5-HT1A and 5-HT2A) and dopamine (D1 and D2) receptors. (R)-Roemerine and (+/-)-nuciferine were found to have high affinity for the 5-HT2A receptor (Ki = 62 and 139 nm, respectively), with (R)-roemerine showing 20- to 400-fold selectivity for the 5-HT2A receptor over the 5-HT1A, D1 and D2 receptors. Investigation into the ligandreceptor interactions suggested that the selectivity of (R)-roemerine is due to it having stronger H-bonding and dipoledipole interactions with several of the key residues in the 5-HT2A receptor-binding site.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Additional Information: | Munusamy, Vani Yap, Beow Keat Buckle, Michael J. C. Doughty, Stephen W. Chung, Lip Yong |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms Haslinda Lahuddin |
| Date Deposited: | 22 Jul 2013 01:06 |
| Last Modified: | 22 Jul 2013 01:06 |
| URI: | http://eprints.um.edu.my/id/eprint/8149 |
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