The morpholino-acetic acid analogue Sch 50911 is a selective GABAB receptor antagonist in rat neocortical slices

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dc.contributor.authorOng, J.
dc.contributor.authorMarino, V.
dc.contributor.authorParker, D.
dc.contributor.authorKerr, D.
dc.contributor.authorBlythin, D.
dc.date.issued1998
dc.description.abstractThe 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.
dc.description.statementofresponsibilityJennifer Ong, Victor Marino, David A.S. Parker, David I.B. Kerr, David J. Blythin
dc.identifier.citationEuropean Journal of Pharmacology, 1998; 362(1):35-41
dc.identifier.doi10.1016/S0014-2999(98)00723-7
dc.identifier.issn0014-2999
dc.identifier.issn1879-0712
dc.identifier.orcidOng, J. [0000-0002-0958-460X]
dc.identifier.urihttp://hdl.handle.net/2440/5991
dc.language.isoen
dc.publisherELSEVIER SCIENCE BV
dc.relation.grantARC
dc.source.urihttps://doi.org/10.1016/s0014-2999(98)00723-7
dc.subjectNeocortex
dc.subjectAnimals
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectBaclofen
dc.subjectMorpholines
dc.subjectGABA Antagonists
dc.subjectDose-Response Relationship, Drug
dc.subjectMale
dc.subjectGABA-B Receptor Antagonists
dc.subjectIn Vitro Techniques
dc.titleThe morpholino-acetic acid analogue Sch 50911 is a selective GABAB receptor antagonist in rat neocortical slices
dc.typeJournal article
pubs.publication-statusPublished

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