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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 it...
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| Published in: | Neuroscience letters 2010-08, Vol.481 (1), p.12-16 |
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| Main Authors: | , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
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| Summary: | 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
. |
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| ISSN: | 0304-3940 1872-7972 |
| DOI: | 10.1016/j.neulet.2010.06.036 |