Association and agonistic action of DN-2327, a novel isoindoline derivative, GABAB receptor in brain.
The association and action of DN-2327, 2-(7-chloro-1,8-naphthyridin-2-yl)-3-[(1,4-dioxa-8- azaspiro[4,5]dec-8-yl)carbonylmethyl]isoindolin-1-one, on the gamma-aminobutyric acid (GABA)B receptor in rat brain have been examined. DN-2327 inhibited the binding of [3H]GABA to GABAB receptor in crude synaptic membrane obtained from rat brain. The Scatchard analysis of [3H]GABA binding to GABAB receptor indicated that DN-2327 induced the decrease in affinity of both high and low affinity binding sites without changing the Bmax values. The forskolin-stimulated adenylate cyclase activity in slices from rat cerebral cortex was significantly suppressed by the addition of DN-2327. Furthermore, this inhibition by DN-2327 was eliminated by the simultaneous additions of 2-hydroxy saclofen or CGP 55845A, GABAB receptor antagonists. These results suggest that DN-2327 may have not only a high association with GABAB receptor but also an agonistic action on the receptor.
Ichida
T
T
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Hirouchi
M
M
Mizutani
H
H
Narihara
R
R
Kuriyama
K
K
D000262:Adenylyl Cyclases / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D054833:Isoindoles; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000187:drug effects*; D013141:Spiro Compounds / Q000494:pharmacology*; D013570:Synaptic Membranes / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D009287:Naphthyridines; D011506:Proteins; D018080:Receptors, GABA-B; D013141:Spiro Compounds; D005680:gamma-Aminobutyric Acid; D000262:Adenylyl Cyclases; C060382:pazinaclone