Protective effects of a novel calcium antagonist with platelet-activating factor-antagonistic action, F-0401, against ischemic brain damage.

Abstract

The protective effects of a novel dihydropyridine calcium antagonist with platelet-activating factor-antagonistic action, F-0401, on ischemic brain damage were investigated using experimental ischemia models in rats and gerbils. F-0401 (1 and 10 mg/kg, i.p.) prevented increases in water content, determined by the wet-dry method, in ischemic areas 24 hr after 1 hr of middle cerebral artery occlusion in the rat. Pretreatment with F-0401 (1 and 10 mg/kg, i.p.) prevented extravasation of Evans blue dye in the brain following 2 hr of bilateral carotid artery occlusion and 2 hr of reperfusion in the rat. Pretreatment with F-0401 (1 and 10 mg/kg, i.p.) protected against neuronal damage to hippocampal CA1 pyramidal cells following 3 and 5 min of forebrain ischemia in the gerbil. Immunostaining against microtubule-associated protein-2 also demonstrated preservation of CA1 neurons in F-0401-treated animals. Thus, this study shows that F-0401 prevents the occurrence of brain edema, disruption of blood-brain barrier and neuronal damage caused by cerebral ischemia. The results demonstrate that F-0401 may be a powerful candidate as a therapeutic agent in the treatment of acute stroke in man.

• Authors: T Chen, H Kato, H Ban, N Nakata, X H Liu, Y Itoyama, K Kogure
• Journal: Archives internationales de pharmacodynamie et de therapie (Arch Int Pharmacodyn Ther) 1994 May-Jun Vol. 327 Issue 3 Pg. 266-78 ISSN: 0003-9780 [Print] Belgium
• PMID: 7848011 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Calcium Channel Blockers
• Dihydropyridines
• Microtubule-Associated Proteins
• Platelet Aggregation Inhibitors
• F 0401
• Evans Blue

Topics

• Animals
• Brain Ischemia (prevention & control)
• Calcium Channel Blockers (administration & dosage, pharmacology, therapeutic use)
• Dihydropyridines (administration & dosage, pharmacology, therapeutic use)
• Disease Models, Animal
• Evans Blue (metabolism)
• Extravasation of Diagnostic and Therapeutic Materials
• Gerbillinae
• Hippocampus (cytology, drug effects, pathology)
• Injections, Intraperitoneal
• Male
• Microtubule-Associated Proteins (metabolism)
• Neurons (cytology, drug effects, pathology)
• Platelet Aggregation Inhibitors (administration & dosage, pharmacology, therapeutic use)
• Prosencephalon (drug effects, pathology)
• Rats
• Rats, Wistar
• Reperfusion Injury (drug therapy)