NPS 1506, a novel NMDA receptor antagonist and neuroprotectant. Review of preclinical and clinical studies.
Ann N Y Acad Sci
; 890: 450-7, 1999.
Article
in En
| MEDLINE
| ID: mdl-10668449
ABSTRACT
NPS 1506 is a moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. NPS 1506 is neuroprotective in rodent models of ischemic stroke, hemorrhagic stroke, and head trauma, with a 2-hr window of opportunity. Neuroprotectant doses of NPS 1506 ranged from approximately 0.1-1.0 mg/kg, with peak plasma concentrations ranging from 8-80 ng/mL. Even at doses producing behavioral toxicity, NPS 1506 did not elicit MK-801-like behaviors, did not generalize to phencyclidine (PCP), and did not elicit neuronal vacuolization. In a Phase I study, intravenous (i.v.) doses of NPS 1506 from 5-100 mg were well tolerated and provided plasma concentrations in excess of those required for neuroprotection in rodents. Adverse events at the 100-mg dose included mild dizziness and lightheadedness, and mild to moderate ataxia. Neither PCP-like psychotomimetic effects nor cardiovascular effects were noted. The long plasma half-life of NPS 1506 (approximately 60 hr) suggests that a single i.v. dose will provide prolonged neuroprotection in humans.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, N-Methyl-D-Aspartate
/
Neuroprotective Agents
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Fluorobenzenes
/
Learning
Limits:
Adolescent
/
Adult
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Animals
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Humans
/
Male
Language:
En
Journal:
Ann N Y Acad Sci
Year:
1999
Document type:
Article
Affiliation country:
United States