LP-211 is a brain penetrant selective agonist for the serotonin 5-HT7 receptor
Copyright policy )LP-211 is a brain penetrant selective agonist for the serotonin 5-HT7 receptor
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.
- Scripps Research Institute United States
- University of Bari Aldo Moro Italy
- Mario Negri Institute for Pharmacological Research Italy
Male, Mice, Knockout, Dose-Response Relationship, Drug, Phenylcarbamates, Brain, Urethane, Piperazines, Body Temperature, Serotonin Receptor Agonists, Mice, Receptors, Serotonin, Animals, Humans, Protein Binding
Male, Mice, Knockout, Dose-Response Relationship, Drug, Phenylcarbamates, Brain, Urethane, Piperazines, Body Temperature, Serotonin Receptor Agonists, Mice, Receptors, Serotonin, Animals, Humans, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).80 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!