| First Author | Hedlund PB | Year | 2010 |
| Journal | Neurosci Lett | Volume | 481 |
| Issue | 1 | Pages | 12-6 |
| PubMed ID | 20600619 | Mgi Jnum | J:163010 |
| Mgi Id | MGI:4820900 | Doi | 10.1016/j.neulet.2010.06.036 |
| Citation | Hedlund PB, et al. (2010) LP-211 is a brain penetrant selective agonist for the serotonin 5-HT(7) receptor. Neurosci Lett 481(1):12-6 |
| abstractText | 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. |
