Partial chemical characterization of cyclopyrrolones ([3H] suriclone) and benzodiazepines ([3H]flunitrazepam) binding site: differences

• Published in: Life sciences (1973) Vol. 36; no. 23; p. 2247
• Main Authors: Zundel, J L, Blanchard, J C, Julou, L
• Format: Journal Article
• Language: English
• Published: Netherlands 10.06.1985
• Subjects: Animals; Ethylmaleimide - pharmacology; Flunitrazepam - metabolism; Hippocampus - metabolism; Imidazoles - pharmacology; In Vitro Techniques; Iodoacetamide - pharmacology; Male; Piperazines - metabolism; Rats; Receptors, GABA-A - drug effects; Receptors, GABA-A - metabolism; Sulfur Compounds; Tetranitromethane - pharmacology; Tritium
• ISSN: 0024-3205
• DOI: 10.1016/0024-3205(85)90336-4

Rat hippocampus membranes were treated with several protein modifying reagents (iodoacetamide, N-ethylmaleimide, tetranitromethane and N-acetylimidazole). The effects of these treatments on the binding sites of cyclopyrrolones ([3H] suriclone), a new chemical family of minor tranquilizers, and benzodiazepines ([3H] flunitrazepam) were investigated. Here we show that both ligands are similarly sensitive to cysteine alkylation: [3H] suriclone and [3H] flunitrazepam binding are reduced by iodoacetamide and slightly increased by N-ethylmaleimide. On the contrary they are clearly differenciated by tyrosine modification: [3H] suriclone binding is not changed whereas [3H] flunitrazepam binding is increased by tetranitromethane and decreased by N-acetylimidazole. Our present findings and published evidence suggest cyclopyrrolones and benzodiazepines bind to distinct sites or to different allosteric forms of the benzodiazepine receptor.