Relative efficacies of 1,4-diazepines on GABA-stimulated chloride influx in rat brain vesicles

Journal Article · Sun Jan 01 00:00:00 EST 1989 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(89)90145-8· OSTI ID:5858007

Ikeda, Masaaki; Weber, K H; Bechtel, W D; Malatynska, E; Yamamura, H I

The effects of 1,4-diazepines with two annelated heterocycles (brotizolam (WE 941), ciclotizolam (WE 973) and WE 1008) on gamma-aminobutyric acid (GABA)-stimulated chloride influx into rat brain membrane vesicles were examined. Brotizolam enhanced GABA-stimulated /sup 36/Cl/sup /minus// influx, while ciclotizolam and WE 1008 showed only a small enhancement of GABA-stimulated /sup 36/Cl/sup /minus// uptake. Brotizolam resulted in a left shift of the GABA dose response curve at lower concentrations of GABA, while at higher concentrations of GABA, brotizolam caused a reduction of the maximal response. The enhancement of GABA-stimulated /sup 36/Cl/sup /minus// uptake by brotizolam was antagonized by Ro 15-1788. At higher concentration of GABA (300 /mu/M), brotizolam inhibited GABA-stimulated /sup 36/Cl/sup /minus// uptake in a dose dependent manner and Ro 15-1788 failed to antagonize this effect.

• Research Organization: Univ. of Arizona Health Sciences Center, Tucson (USA)
• OSTI ID: 5858007
• Journal Information: Life Sci.; (United States), Vol. 45:4
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AMINOBUTYRIC ACID
BIOCHEMICAL REACTION KINETICS
CHLORIDES
MEMBRANE TRANSPORT
TRANQUILIZERS
BIOLOGICAL EFFECTS
BRAIN
CELL MEMBRANES
CHLORINE 36
DOSE-RESPONSE RELATIONSHIPS
RATS
TRACER TECHNIQUES
AMINO ACIDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CHLORINE COMPOUNDS
CHLORINE ISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HALIDES
HALOGEN COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PSYCHOTROPIC DRUGS
RADIOISOTOPES
REACTION KINETICS
RODENTS
VERTEBRATES
YEARS LIVING RADIOISOTOPES
550201* - Biochemistry- Tracer Techniques