caa a22 4500 469077913 CHVBK 20180323132940.0 cr unu---uuuuu 170328e19920701xx s 000 0 eng 10.1007/BF00167563 doi (NATIONALLICENCE)springer-10.1007/BF00167563 Molecular structural basis of ligand selectivity for 5-HT2 versus 5-HT1C cortical receptors [Elektronische Daten] [Pamela Pierce, Joanne Kim, Stephen Peroutka] Summary: A molecular structural criterion of ligand selectivity for the 5-HT2 versus 5-HT1C receptor was hypothesized on the basis of radioligand binding data. Despite the large number of compounds which have been tested at both receptors, analysis of published data led to the identification of only five agents which are greater than 10-fold selective for the 5-HT2 versus the 5-HT1C receptor. Comparison of the two-dimensional structures revealed that, although these five compounds represent three distinct structural classes, they share a common structural feature located in the region hypothesized to be involved in receptor binding: a carbonyl or carboxyl oxygen interposed spatially between an aromatic ring and nitrogen atom. This structural feature was used to predict the relative selectivity of compounds that had not previously been analyzed at both the 5-HT2 and 5-HT1C receptors. All six drugs tested which contain the identified reactive carbonyl or carboxyl group were found to be selective for the 5-HT2 versus the 5-HT1C receptor with selectivity ratios ranging from 26 to 380. By contrast, three agents which are structurally similar but do not contain the reactive carbonyl or carboxyl group displayed equally high affinity for both receptor binding sites. Since the physiological roles of the 5-HT2 and 5-HT1C receptor are markedly different, it would be of potential clinical and scientific value to utilize this molecular structural feature to further identify chemical compounds which would selectively interact with only one of the two receptors. Springer-Verlag, 1992 5-HT2 receptor nationallicence 5-HT1C receptor nationallicence 5-HT ligand selectivity nationallicence Pierce Pamela Department of Neurology, Stanford University School of Medicine, 94305, Stanford, CA, USA aut Kim Joanne Department of Neurology, Stanford University School of Medicine, 94305, Stanford, CA, USA aut Peroutka Stephen Department of Neurology, Stanford University School of Medicine, 94305, Stanford, CA, USA aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/1(1992-07-01), 4-11 0028-1298 346:1<4 1992 346 210 https://doi.org/10.1007/BF00167563 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00167563 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pierce Pamela Department of Neurology, Stanford University School of Medicine, 94305, Stanford, CA, USA aut NATIONALLICENCE 700 1- Kim Joanne Department of Neurology, Stanford University School of Medicine, 94305, Stanford, CA, USA aut NATIONALLICENCE 700 1- Peroutka Stephen Department of Neurology, Stanford University School of Medicine, 94305, Stanford, CA, USA aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/1(1992-07-01), 4-11 0028-1298 346:1<4 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer