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|Title:||The morpholino-acetic acid analogue Sch 50911 is a selective GABAB receptor antagonist in rat neocortical slices|
|Citation:||European Journal of Pharmacology, 1998; 362(1):35-41|
|Publisher:||ELSEVIER SCIENCE BV|
|Jennifer Ong, Victor Marino, David A.S. Parker, David I.B. Kerr, David J. Blythin|
|Abstract:||The pharmacological properties of (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid (Sch 50911) were evaluated on GABA(B) receptors in rat neocortical slices. The GABA(B) receptor agonist, baclofen, produced a concentration-dependent depression of the frequency of spontaneous discharges in slices maintained in Mg2+-free Krebs medium with an EC50 of 6 microM, reversibly antagonised by Sch 50911 (5, 10 and 25 microM) with an apparent pA2 of 6.0 +/- 0.1. The (-) enantiomer Sch 50910 (500 microM) and the racemic des-methyl analogue Sch 48588 (500 microM) were inactive. In slices preloaded with [3H]GABA, Sch 50911 antagonised GABA(B) autoreceptors, increasing the electrically-stimulated 3H overflow in a concentration-dependent manner, with an IC50 of 3 microM. The maximal effect (148 +/- 10.5%) was found at 10 microM, but at 50 microM the response was reduced to 67 +/- 19%. In contrast, evoked release was unaffected by Sch 50910 (100 microM) whilst Sch 48588 at 100 microM increased the overflow by 51.3 +/- 11.6%. In summary, Sch 50911 is a relatively potent antagonist of considerable potential in studies of GABA(B) receptor function.|
|Keywords:||Neocortex; Animals; Rats; Rats, Sprague-Dawley; Baclofen; Morpholines; GABA Antagonists; Dose-Response Relationship, Drug; Male; GABA-B Receptor Antagonists|
|Appears in Collections:||Anaesthesia and Intensive Care publications|
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