Anxiolytic properties of the selective, non-peptidergic CRF(1) antagonists, CP154,526 and DMP695: a comparison to other classes of anxiolytic agent.
The selective, non-peptidergic corticotropin-releasing factor (CRF)(1) receptor antagonists, CP154,526 and DMP695, dose-dependently increased punished responses of rats in a Vogel conflict test and enhanced social interaction (SI) of rats in an unfamiliar environment. They were, however, inactive in a plus-maze procedure and failed to reduce ultrasonic vocalizations (USV) associated with an aversive environment. In contrast, the benzodiazepine, chlordiazepoxide, was effective in all these procedures. Further, the serotonin (5-HT)(1A) agonist, flesinoxan, was active in each paradigm (except the plus-maze) while the 5-HT(2C) antagonist, SB242,084, was effective in the SI and Vogel but not the plus-maze and USV procedures. In contrast to chlordiazepoxide, flesinoxan and SB242,084, CP154,526 did not modify dialysate levels of 5-HT, norepinephrine (NE) and dopamine (DA) in the frontal cortex (FCX) of freely moving rats. In conclusion, CP154,526 and DMP695 possess a common and distinctive profile of anxiolytic action expressed in the absence of an intrinsic influence upon monoamine release.
Millan
M J
MJ
Psychopharmacology Department, Institut de Recherches Servier, Centre de Recherches de Croissy, Paris, France. mark.millan@fr.netgrs.com
Brocco
M
M
Gobert
A
A
Dorey
G
G
Casara
P
P
Dekeyne
A
A
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007398:Interpersonal Relations; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D004856:Postural Balance / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012701:Serotonin / Q000378:metabolism; D014828:Vocalization, Animal / Q000187:drug effects; D000099052:CRF Receptor, Type 1
C437952:(N-(2-chloro-4,6-dimethylphenyl)-1-(1-methoxymethyl)-(2-methoxymethyl)-6-methyl-1H-1,2,3-triazolo(4,5-c)pyridin-4-amine) mesylate; D014151:Anti-Anxiety Agents; C101628:CP 154526; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D012701:Serotonin; D000099052:CRF Receptor, Type 1; D004298:Dopamine; D009638:Norepinephrine