Abstract
Using grease-gap recording from rat neocortical slices, the GABA B receptor agonist baclofen elicited reversible and concentration-dependent hyperpolarizing responses (EC 50=18±2.3 μM). 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 (EC 50=2±0.5 μM). In slices preincubated with either [ 3H]GABA or [ 3H]glutamic acid, 3-Cl,4-MeO-fendiline (1 μM) potentiated the inhibitory effect of baclofen (2 μM) 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 μM, without affecting the basal release. These effects were blocked by Sch 50911 (10 μM). Our findings suggest that 3-Cl,4-MeO-fendiline is a potent potentiator of pre- and postsynaptic GABA B receptor-mediated functions.
Published Version
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