Amoxapine inhibition of GABA-stimulated chloride conductance: Investigations of potential sites of activity

Journal Article · Sun Jan 01 04:00:00 EST 1989 · Life Sciences; (USA)

DOI:https://doi.org/10.1016/0024-3205(89)90544-4· OSTI ID:7027108

Ikeda, M; Knapp, R J; Yamamura, H I ^[1]; Malatynska, E ^[2]

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1. Univ. of Arizona, Tucson (USA)
2. Ohio State Univ., Columbus (USA)

Amoxapine inhibits GABA-stimulated chloride conductance by acting on the GABA{sub A}-receptor chloride-ionophore complex which can be studied using membrane vesicles prepared from rat cerebral cortex. Amoxapine produces a right shift in the GABA concentration-response curve for the stimulation of {sup 36}Cl{sup {minus}} uptake into these vesicles with no apparent change in the maximum response. Schild analysis of these data gave a pA{sub 2} value of 5.52 with a slope of 0.79. Amoxapine inhibits the binding of the GABA{sub A} receptor selective antagonist ({sup 3}H)SR 95531 with an IC{sub 50} value of 3.45 {mu}M and a pseudo Hill coefficient of 0.83. In contrast, 10 {mu}M amoxapine inhibits ({sup 3}H) flunitrazepam binding by less than 25% while the benzodiazepine antagonist Ro 15-1788 reduces the amoxapine inhibition of GABA-stimulated chloride conductance only at high concentrations.

• OSTI ID: 7027108
• Journal Information: Life Sciences; (USA), Journal Name: Life Sciences; (USA) Vol. 45:20; ISSN 0024-3205; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

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