Literature DB >> 20600619

LP-211 is a brain penetrant selective agonist for the serotonin 5-HT(7) receptor.

Peter B Hedlund1, Marcello Leopoldo, Silvio Caccia, Gor Sarkisyan, Claudia Fracasso, Giuliana Martelli, Enza Lacivita, Francesco Berardi, Roberto Perrone.   

Abstract

We have determined the pharmacological profile of the new serotonin 5-HT(7) receptor agonist N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (LP-211). Radioligand binding assays were performed on a panel of 5-HT receptor subtypes. The compound was also evaluated in vivo by examining its effect on body temperature regulation in mice lacking the 5-HT(7) receptor (5-HT(7)(-/-)) and their 5-HT(7)(+/+) sibling controls. Disposition studies were performed in mice of both genotypes. It was found that LP-211 was brain penetrant and underwent metabolic degradation to 1-(2-diphenyl)piperazine (RA-7). In vitro binding assays revealed that RA-7 possessed higher 5-HT(7) receptor affinity than LP-211 and a better selectivity profile over a panel of 5-HT receptor subtypes. In vivo it was demonstrated that LP-211, and to a lesser degree RA-7, induced hypothermia in 5-HT(7)(+/+) but not in 5-HT(7)(-/-) mice. Our results suggest that LP-211 can be used as a 5-HT(7) receptor agonist in vivo. 2010 Elsevier Ireland Ltd. All rights reserved.

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Year:  2010        PMID： 20600619      PMCID： PMC2910240          DOI： 10.1016/j.neulet.2010.06.036

Source DB:  PubMed          Journal:  Neurosci Lett        ISSN： 0304-3940            Impact factor:   3.046


  24 in total

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