| Autor: |
Ghisdal, Philippe, Noel, Nadine, Pacico, Nathalie, Martini, Murielle, Foerch, Patrik, Hanon, Etienne, Wolff, Christian |
| Zdroj: |
SLAS Discovery: Advancing Life Sciences R&D; March 2014, Vol. 19 Issue: 3 p462-467, 6p |
| Abstrakt: |
Gamma amino butyric acid receptors (GABA) are major therapeutic targets for the development of drugs in neurological and psychiatric disorders. The new generation of GABAAmodulators is targeting subtype selectivity and low/partial efficacy on the receptor to potentially overcome the adverse effects described for drugs with full agonist profile. We evaluated a screening approach to measure the relative efficacy of GABAApositive allosteric modulators (PAM) using automated patch clamp and fluorescence membrane potential assays. We determined that the use of an internal comparator (zolpidem), tested on each cell in parallel to the test compound, provides a reliable approach to measure and compare the relative efficacy of PAM ligands. Patch clamp recordings on recombinant GABAAreceptors, using a multiple drug addition protocol, allows us to rank PAM ligands with different levels of efficacies. We observed that fluorescence membrane potential assays are not predictive of the relative efficacies of GABAAPAM ligands. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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