3-Chloro,4-methoxyfendiline is a potent GABA(B) receptor potentiator in rat neocortical slices.
Using grease-gap recording from rat neocortical slices, the GABA(B) receptor agonist baclofen elicited reversible and concentration-dependent hyperpolarizing responses (EC50=18+/-2.3 microM). The hyperpolarizations were antagonised by the GABA(B) receptor antagonist Sch 50911 [(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid). (+)-N-1-(3-chloro-4-methoxyphenyl)ethyl-3,3-diphenylpropylamine (3-chloro,4-methoxyfendiline; 3-Cl,4-MeO-fendiline) reversibly potentiated baclofen-induced hyperpolarizing responses, which were reduced by Sch 50911, producing leftward shifts of the baclofen concentration-response curves, with a marked increase in the maximal hyperpolarization (EC50=2+/-0.5 microM). In slices preincubated with either [3H]GABA or [3H]glutamic acid, 3-Cl,4-MeO-fendiline (1 microM) potentiated the inhibitory effect of baclofen (2 microM) on the electrically evoked release of [3H]GABA and had a similar effect on the release of [3H]glutamic acid at a concentration of 0.5 microM, without affecting the basal release. These effects were blocked by Sch 50911 (10 microM). Our findings suggest that 3-Cl,4-MeO-fendiline is a potent potentiator of pre- and postsynaptic GABA(B) receptor-mediated functions.
Ong
Jennifer
J
Department of Anaesthesia and Intensive Care, The University of Adelaide, Adelaide, South Australia 5005, Australia. jennifer.ong@adelaide.edu.au
Parker
David A S
DA
Marino
Victor
V
Kerr
David I B
DI
Puspawati
Ni Made
NM
Prager
Rolf H
RH
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005275:Fendiline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D019579:Neocortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; C502248:3-Chloro-4-methoxyfendiline; D058786:GABA-B Receptor Agonists; D009025:Morpholines; D018080:Receptors, GABA-B; D001418:Baclofen; D005275:Fendiline