The enhancement of muscimol-stimulated 36C1 influx by the antispastic 5-aryl-3-(alkylsulfonyl)-4H-1,2,4-triazole (MDL 27,531) in rat brain membrane vesicles.
The antispastic triazole, 4-methyl-3-methylsulphonyl-5-phenyl-4H-1,2,4-triazole (MDL 27,531) was tested in glycine- and muscimol-stimulated 36Cl- influx into brain membrane preparations. MDL 27,531 (100 nM) had no effect on glycine- (100 nM-400 microM) stimulated 36Cl- influx in brain stem tissue; on the other hand, MDL 27,531 (10 nM-10 microM) enhanced muscimol- (1 microM) stimulated 36Cl- influx in cerebellar but not cortical membranes. In the presence of the benzodiazepine (BZD) antagonist, flumazenil (10 microM), MDL 27,531 inhibited muscimol-stimulated flux. These data suggest a novel interaction of this triazole with subtypes of the gamma-aminobutyric acid (GABA)A receptor complex and the BZD receptor.
Miller
J A
JA
Marion Merrell Dow Research Institute, Cincinnati, OH 45215, USA.
Braun
D
D
Chmielewski
P A
PA
Kane
J M
JM
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism*; D002713:Chlorine; D005445:Flunitrazepam / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009118:Muscimol / Q000494:pharmacology*; D011868:Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018118:Chloride Channels; D018755:GABA Agonists; D018757:GABA Modulators; D011868:Radioisotopes; D011963:Receptors, GABA-A; D014230:Triazoles; C077362:4-methyl-3-methylsulfonyl-5-phenyl-4H-1,2,4-triazole; D009118:Muscimol; D002713:Chlorine; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D005998:Glycine