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Comparative potencies of CGP 47654A and CGP 46165A as GABA(B) receptor antagonists in rat brain.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 1999 Jun 25; Vol. 374 (3), pp. 351-4. - Publication Year :
- 1999
-
Abstract
- In rat neocortical slices maintained in Mg2+-free Krebs medium, the gamma-aminobutyric acid (GABAB) receptor agonist baclofen concentration-dependently depressed the frequency of spontaneous discharges (EC50 = 6.1 microM). This was reversibly antagonised by 3-aminopropyl-(1,1-difluoro-n-butyl)-phosphinic acid (25, 100, 500 microM) (CGP 47654A) and 3-aminopropyl-P-(alpha-hydroxybenzyl)-phosphinic acid (CGP 46165A) (50, 100, 400 microM) which produced rightwards shifts of the baclofen concentration-response curves, with respective pA2 values of 4.9+/-0.2 and 4.6+/-0.15. Although relatively potent on GABAB heteroreceptors studied here, CGP 47654A and CGP 46165A were 5 and 50 times weaker, respectively, as GABAB autoreceptor antagonists [Froestl, W., Mickel, S.J., Von Sprecher, G., Diel, P.J., Hall, R.G., Maier, L., Strub, D., Melillo, V., Baumann, P.A., Bernasconi, R., Gentsch, C., Hauser, K., Jaekel, J., Karlsson, G., Klebs, K., Maitre, L., Marescaux, C., Pozza, M.F., Schmutz, M., Steinmann, M.W., Van Riezen, H., Vassout, A., Mondadori, C., Olpe, H.R., Waldmeier, P.C., Bittiger, H., 1995. Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists. J. Med. Chem. 38: 3313-3331.], representing potentially useful ligands for differentiating GABA hetero- and autoreceptors.
- Subjects :
- Animals
Baclofen pharmacology
Brain metabolism
Dose-Response Relationship, Drug
GABA Agonists pharmacology
In Vitro Techniques
Male
Neocortex drug effects
Neocortex metabolism
Phosphinic Acids chemistry
Rats
Rats, Sprague-Dawley
Tritium
gamma-Aminobutyric Acid drug effects
gamma-Aminobutyric Acid metabolism
Brain drug effects
GABA-B Receptor Antagonists
Phosphinic Acids pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 374
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 10422779
- Full Text :
- https://doi.org/10.1016/s0014-2999(99)00377-5