CGP 36216 is a selective antagonist at GABA(B) presynaptic receptors in rat brain.
In rat neocortical preparations maintained in Mg(2+)-free Krebs medium, baclofen depressed the frequency of spontaneous discharges in a concentration-dependent manner (EC(50) = 6 microM), sensitive to (3-aminopropyl)ethylphosphinic acid (CGP 36216) (100, 300 and 500 microM) (pA(2) = 3.9 +/- 0.1). By contrast, CGP 36216, up to 1 mM, was ineffective in antagonising baclofen-induced hyperpolarisations, mediated through gamma-aminobutyric acid(B) (GABA(B)) postsynaptic receptors. In electrically stimulated brain slices preloaded with [3H]GABA, CGP 36216 increased [3H]GABA release (IC(50) = 43 microM), which was reversed by baclofen (20 microM). While CGP 36216 is ineffective at GABA(B) postsynaptic receptors, it is appreciably more active at presynaptic receptors.
Ong
J
J
Department of Anaesthesia and Intensive Care, The University of Adelaide, South Australia 5005, Adelaide, Australia. jennifer.ong@adelaide.edu.au
Bexis
S
S
Marino
V
V
Parker
D A
DA
Kerr
D I
DI
Froestl
W
W
D000818:Animals; D017660:Autoreceptors / Q000187:drug effects* / Q000378:metabolism; D001418:Baclofen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D008297:Male; D019579:Neocortex / Q000187:drug effects* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology; D010721:Phosphinic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism
D017660:Autoreceptors; C434276:CGP 36216; D018755:GABA Agonists; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D010721:Phosphinic Acids; D018080:Receptors, GABA-B; C068457:3-aminopropyl(methyl)phosphinic acid; D005680:gamma-Aminobutyric Acid; D001418:Baclofen