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Comparative activities of the enantiomeric GABA(B) receptor agonists CGP 44532 and 44533 in central and peripheral tissues.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2001 Jan 19; Vol. 412 (1), pp. 27-37. - Publication Year :
- 2001
-
Abstract
- In neocortical slices maintained in Mg(2+)-free Krebs medium, the gamma-aminobutyric acid (GABA(B)) receptor agonists baclofen, (3-amino-2(S)-hydroxypropyl)methylphosphinic acid (CGP 44532), and its (R)-enantiomer CGP 44533 depressed the frequency of spontaneous discharges in a concentration-dependent manner (EC(50)=10, 6.5, and 50 microM, respectively). These effects were reversibly antagonised by the GABA(B) receptor antagonist (+)-(S)-5,5 dimethylmorpholinyl-2-acetic acid (Sch 50911) (3, 10, and 30 microM) (average pA(2) value=6.0+/-0.2). In neocortical wedges, baclofen, CGP 44532 and CGP 44533 elicited concentration-dependent hyperpolarisations (the EC(50)s were 14, 7.5 and 16 microM, respectively) sensitive to Sch 50911 (1, 5, 10 microM) (average pA(2) value=6.0+/-0.1), whilst they also depressed ileal electrically elicited cholinergic twitch contractions (EC(50)=11, 7, and 50 microM) that were antagonised by Sch 50911 (average pA(2) value=6.0+/-0.1). In electrically stimulated brain slices preloaded with [3H]GABA, baclofen, CGP 44532 and CGP 44533 decreased [3H]GABA release (IC(50)=5, 0.45, and 10 microM); this effect was reversed by Sch 50911 (50 microM). It is concluded that CGP 44532 is a far more potent agonist at GABA(B) autoreceptors than at central or peripheral heteroreceptors.
- Subjects :
- Animals
Dose-Response Relationship, Drug
Guinea Pigs
Ileum physiology
Male
Neocortex physiology
Phosphinic Acids
Rats
Rats, Sprague-Dawley
Receptors, GABA-B physiology
Baclofen pharmacology
GABA-B Receptor Agonists
Ileum drug effects
Neocortex drug effects
Organophosphonates pharmacology
gamma-Aminobutyric Acid analogs & derivatives
gamma-Aminobutyric Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 412
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 11166733
- Full Text :
- https://doi.org/10.1016/s0014-2999(00)00945-6