Preclinical pharmacology of B-20991, a 5-HT1A receptor agonist with anxiolytic activity.
The purpose of this study was to characterize the pharmacological effects of 2-[[4-(o-methoxyphenyl)piperazin-1-yl]methyl]-1,3-dioxoperhydro imidazo[1,5-a]pyridine (B-20991) by using several biochemical and behavioral assays. Results of binding studies showed that B-20991 binds with high affinity to the 5-HT1A receptor (Ki = 31.7 +/- 1.7 nM), moderate affinity to 5-HT3 receptor (Ki = 269.4 +/- 23.2 nM) and low affinity (Ki > 1000) to 5-HT2A receptor, dopamine D2 receptor, benzodiazepine receptors and alpha1-adrenoceptor. The administration of B-20991 produced a dose and time related decrease in mouse rectal temperature, increased both lower lip retraction and flat body posture behavioral scores in rat, decreased 5-hydroxytryptamine (5-HT, serotonin) neuronal activity in mouse hypothalamus, and did not alter dopamine neuronal activity nor locomotor activity. The anxiolytic activity of B-20991 was assessed by using both the social interaction and light/dark box tests. The results of these tests indicated that B-20991 caused a dose-related increase in the social interaction and light/dark box behavioral scores. Taken together, these results suggest that B-20991 is a 5-HT1A receptor agonist that exhibits anxiolytic activity.
Beneytez
M E
ME
Departamento de Farmacología, Facultad de Farmacia and Instituto Pluridisciplinar, Universidad Complutense, Madrid, Spain.
López Rodríguez
M L
ML
Rosado
M L
ML
Morcillo
M J
MJ
Orensanz
L
L
Fuentes
J A
JA
Manzanares
J
J
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; C112914:B 20991; D007093:Imidazoles; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists