Preclinical anticonvulsant and neuroprotective profile of 8319, a non-competitive NMDA antagonist
- Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ (USA)
8319, ((+-)-2-Amino-N-ethyl-alpha- (3-methyl-2-thienyl) benzeneethanamine 2HCl), is a novel compound with the profile of a non-competitive NMDA antagonist. The compound displaced (3H) TCP with high affinity (IC50 = 43 nM), but was inactive at the NMDA, benzodiazepine and GABA sites; in vivo, 8319 showed good efficacy as an anticonvulsant and potential neuroprotective agent. It blocked seizures induced by NMDLA, supramaximal electroshock, pentylenetetrazol (PTZ), picrotoxin, and thiosemicarbazide with ED50's of 1-20 mg/kg ip. As a neuroprotective agent, 8319 (30-100 mg/kg sc) prevented the death of dorsal hippocampal pyramidal cells induced by direct injection of 20 nmol NMDA. At 15 mg/kg ip, the compound was also effective against hippocampal neuronal necrosis induced via bilateral occlusion of the carotid arteries in gerbils. In summary, 8319 is a noncompetitive NMDA antagonist with good anticonvulsant activity and may possess neuroprotective properties useful in the treatment of brain ischemia.
- OSTI ID:
- 5659738
- 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
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550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANEMIAS
ANTICONVULSANTS
ASPARTIC ACID
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARBOXYLIC ACIDS
CARDIOVASCULAR DISEASES
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMOTHERAPY
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
HEMIC DISEASES
HYDROGEN COMPOUNDS
ISCHEMIA
ISOTOPE APPLICATIONS
KINETICS
MEMBRANE PROTEINS
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RECEPTORS
SYMPTOMS
THERAPY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASCULAR DISEASES