The affinity of cyclodepsipeptides to the brain chloride channel domain of the GABAA receptor in vitro.

The y-aminobutyric acid (GABAA) receptor is part of a supramolecular complex which is responsible for gating a chloride channel in the brain.1} Several different classes of compounds interact with this complex, e.g. 1 ,4-benzodiazepines, barbiturates, some steroids, and f-butylbicyclophosphorothionate (TBPS). The convulsant picrotoxin2) and the diterpenes carnosol and carnosic acid3) bind to the same site as TBPS. In a search for fungal metabolites that bind to the TBPSsite, extracts of more than 100 species were screened for their ability to inhibit 35S-TBPS binding to a rat brain membrane homogenate preparation (unpublished results), with a sensitive radio-ligand assay.40 One of the most potent extracts was obtained from a Fusarium species, and bioassay-guided