Preclinical anxiolytic profiles of 7189 and 8319, novel non-competitive NMDA antagonists

Journal Article · Sun Dec 31 23:00:00 EST 1989 · Progress in Clinical and Biological Research; (USA)

OSTI ID:5962740

Dunn, R W; Corbett, R; Martin, L L; Payack, J F; Laws-Ricker, L; Wilmot, C A; Rush, D K; Cornfeldt, M L; Fielding, S ^[1]

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1. Hoechst-Roussel Pharmaceuticals, Inc. Somerville, NJ (USA)

Antagonists at excitatory amino acid receptors, especially the N-methyl-d-aspartate (NMDA) subtype, have been shown to possess anticonvulsant and anxiolytic properties. Two closely related benzeneethanamines, are potential novel anxiolytic agents which bind with high affinity to the NMDA receptor at the non-competitive site and are relatively non-toxic (LD50's-160 mg/kg, ip). 7189 and 8319 showed anxiolytic effects in schedule controlled conflict assays as well as in the social interaction (SI) and elevated plus maze (EPM) procedures in rats. Following intraperitoneal administration of 7189 at 20 to 60 mg/kg, conflict responding was increased from 2- to 7-fold in the modified Cook and Davidson and Geller conflict paradigms. 8319, at 2.5 to 5 mg/kg, produced a two fold increase in conflict responding. In the non-schedule controlled procedures, 7189 at 20 mg/kg increased SI time by 23% while in the EPM at 10 to 20 mg/kg, open arm exploration time increased by 41 to 77%. Likewise, 8319 at 2.5 and 5 mg/kg increased open arm exploration and SI time by 50 and 37%, respectively. In summary, 7189 and 8319 were efficacious in four behavioral procedures predictive of potential anxiolytic agents. Although these compounds have not been submitted for clinical evaluation, they may represent a new class of beneficial compounds for the treatment of anxiety.

• OSTI ID: 5962740
• Journal Information: Progress in Clinical and Biological Research; (USA), Journal Name: Progress in Clinical and Biological Research; (USA) Vol. 361; ISSN PCBRD; ISSN 0361-7742
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
ANTICONVULSANTS
ASPARTIC ACID
BEHAVIOR
BIOCHEMICAL REACTION KINETICS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LEARNING
MAMMALS
MEMBRANE PROTEINS
MICE
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES