Saclofen (the direct sulphonic analogue of baclofen) is a competitive antagonist of baclofen at GABAB receptors in guinea pig ileum and rat cortical slices (estimated pA2 = 5.3), at least twice as potent as 2-hydroxy-saclofen (pA2 = 5)[1]. 2-hydroxy-saclofen (2-OH-S), a sulphonic analogue of baclofen, slightly increased the twitch height and reversibly antagonised the GABA- and baclofen-induced depression of twitch contractions in the guinea pig vas deferens and isolated ileum, causing a parallel dextral shift in the baclofen dose-response curve in a competitive manner (pA2 = 5.0) in the latter tissue. 2-OH-S (10-50 mM) reversibly elevated the spike height and antagonised the baclofen (8-20 mM)-induced suppression of ictal discharges in rat cortical slices superfused in Mg2+-free Krebs solution, the spike height declining to control level within 15 min of washout[2]. Baclofen (2-hydroxy-saclofen) (0.5-20 mM) reduces the amplitude of excitatory postsynaptic potentials (EPSPs) recorded from hippocampal CA1 pyramidal neurons. In the presence of 200-500 mM 2-OH-S, the synaptic depressant action of baclofen is significantly reduced[3].
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