Correlating the metabolic stability of psychedelic 5-HT2A agonists with anecdotal reports of human oral bioavailability.
Neurochem Res
; 39(10): 2018-23, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24519542
ABSTRACT
2,5-Dimethoxyphenethylamines and their N-benzylated derivatives are potent 5-HT2A agonists with psychedelic effects in humans. The N-benzylated derivatives are among the most selective 5-HT2A agonists currently available and their usage as biochemical and brain imaging tools is increasing, yet very little is known about the relationships between the structure of the ligands and their pharmacokinetic profile. In order to evaluate the potential of these compounds for in vivo applications we have determined the microsomal stability of 11 phenethylamines and 27 N-benzylated derivatives thereof using human liver microsomes. We found that the N-benzylated phenethylamines have much higher intrinsic clearance than the parent phenethylamines. We hypothesize that their low hepatic stability renders them orally inactive due to first pass metabolism, which is supported by anecdotal data from recreational use of these compounds.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Agonistas do Receptor de Serotonina
/
Receptor 5-HT2A de Serotonina
Limite:
Humans
Idioma:
En
Revista:
Neurochem Res
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Dinamarca