Agonist activity of a novel compound, 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554), at central 5-HT1A receptors.
We used an in vitro radioligand receptor binding assay with rat cerebral cortex, hippocampus and striatum membrane preparations to show that 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554) had much higher affinity for 5-HT1A recognition sites than for 5-HT1-non-A, 5-HT2, benzodiazepine, dopamine D-2 and alpha 2-adrenergic recognition sites. The compound inhibited the activity of forskolin-stimulated adenylate cyclase in rat hippocampal membranes. Intraperitoneal injection of BP-554 to mice decreased the concentration of only 5-hydroxy-indoleacetic acid of the amines and their metabolites in the brain and decreased the accumulation of 5-hydroxytryptophan in the brain after decarboxylase inhibition by 3-hydroxybenzylhydrazine. Furthermore, the administration of BP-554 caused hypothermia and increased serum corticosterone levels in mice. The observed effects of BP-554 were similar to those of 8-hydroxy-2-(di-n-propylamino)tetralin. These results suggest that BP-554 acts as a selective 5-HT1A receptor agonist in vivo.
Matsuda
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Seong
Y H
YH
Aono
H
H
Kanda
T
T
Baba
A
A
Saito
K
K
Tobe
A
A
Iwata
H
H
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000588:Amines / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005576:Colforsin / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010879:Piperazines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000588:Amines; D010879:Piperazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D005576:Colforsin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C062718:BP 554; D000262:Adenylyl Cyclases; D003345:Corticosterone