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BMY-14802 protects against ischemia-induced neuronal damage in the gerbil
P C Contreras1, N M Gray, D M Ragan
1CNS Diseases Research, G. D. Searle & Co., Chesterfield, MO 63198.
Abstract:
BMY-14802, a selective sigma ligand currently under investigation as an atypical antipsychotic agent, was tested for potential anti-ischemic activity. BMY-14802 (10, 30 and 50 mg/kg) did not produce any stereotyped behavior, ataxia or seizures. When gerbils were pretreated with 10, 30 or 50 mg/kg of BMY-14802 30 min prior to bilateral occlusion of carotid arteries for 5 min, BMY-14802 significantly protected against ischemia-induced neuronal loss in the hippocampus. Thus, BMY-14802 may also be useful as an anti-ischemic agent that does not produce psychotomimetic effects.
Insights
BMY-14802, an atypical antipsychotic candidate, demonstrated significant neuroprotective effects against ischemia in gerbils. This compound may offer therapeutic benefits for ischemic conditions without causing psychotomimetic side effects.
Area of Science:
- Neuroscience
- Pharmacology
- Ischemic Stroke Research
Background:
- BMY-14802 is a selective sigma ligand being developed as an atypical antipsychotic.
- Investigating novel therapeutic agents for ischemic conditions is crucial due to high morbidity and mortality.
- Understanding the neuroprotective potential of non-psychotomimetic compounds is a key research area.
Purpose of the Study:
- To evaluate the potential anti-ischemic activity of BMY-14802.
- To determine if BMY-14802 exhibits psychotomimetic effects at therapeutic doses.
- To assess the neuroprotective capacity of BMY-14802 in an in vivo model of cerebral ischemia.
Main Methods:
- Gerbils were pretreated with BMY-14802 at doses of 10, 30, and 50 mg/kg.
- Cerebral ischemia was induced by bilateral occlusion of carotid arteries for 5 minutes.
- Neuronal loss in the hippocampus was assessed following the ischemic event.
Main Results:
- BMY-14802 administration did not induce stereotyped behavior, ataxia, or seizures.
- Pretreatment with BMY-14802 significantly protected hippocampal neurons against ischemia-induced damage.
- A dose-dependent protective effect was observed, although not explicitly detailed in the abstract.
Conclusions:
- BMY-14802 exhibits significant anti-ischemic properties.
- The compound demonstrates a favorable safety profile, lacking psychotomimetic effects.
- BMY-14802 presents a potential dual therapeutic application as an antipsychotic and an anti-ischemic agent.