Synthesis and characterization of a series of diarylguanidines that are noncompetitive N-methyl-D-aspartate receptor antagonists with neuroprotective properties

Journal Article · Sat Jul 01 00:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.14.5631· OSTI ID:5228160

Keana, J F.W.; McBurney, R N; Scherz, M W; Fischer, J B; Hamilton, P N; Smith, S M; Server, A C; Finkbeiner, S; Stevens, C F; Jahr, C; Weber, E ^[1]

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1. Univ. of Oregon, Eugene (USA)

Four diarylguanidine derivatives were synthesized. These compounds were found to displace, at submicromolar concentrations, {sup 3}H-labeled 1-(1-(2-thienyl)cyclohexyl)piperidine and (+)-({sup 3}H)MK-801 from phencyclidine receptors in brain membrane preparations. In electrophysiological experiments the diarylguanidines blocked N-methyl-D-aspartate (NMDA)-activated ion channels. These dairylguanidines also protected rat hippocampal neurons in vitro from glutamate-induced cell death. The results show that some diarylguanidines are noncompetitive antagonists of NMDA receptor-mediated responses and have the neuroprotective property that is commonly associated with blockers of the NMDA receptor-gated cation channel. Diarylguanidines are structurally unrelated to known blockers of NMDA channels and, therefore, represent a new compound series for the development of neuroprotective agents with therapeutic value in patients suffering from stroke, from brain or spinal cord trauma, from hypoglycemia, and possibly from brain ischemia due to heart attack.

• OSTI ID: 5228160
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:14; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GUANIDINES
DERIVATIZATION
RECEPTORS
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
BRAIN
CELL MEMBRANES
HIPPOCAMPUS
MOLECULAR STRUCTURE
NERVE CELLS
RADIORECEPTOR ASSAY
RATS
TRITIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
BODY
CARBONIC ACID DERIVATIVES
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RODENTS
SOMATIC CELLS
SYNTHESIS
TRACER TECHNIQUES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques