Anti-ischemic effect of the novel anti-ischemic agent 2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride and possible mechanism of its action.

Abstract

The protective effect of E-2001 (2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride) was examined in various ischemic models, and the mechanisms of its action were investigated in vitro and in vivo. 1. Pretreatment with E-2001 ameliorated the degeneration of pyramidal neurons in the hippocampal CA1 sector following transient ischemia in Mongolian gerbils. 2. E-2001 improved stroke symptoms induced by permanent unilateral carotid artery ligation in gerbils. 3. E-2001 prolonged the survival time following permanent bilateral carotid artery ligation in gerbils and mice. E-2001 also prolonged the survival time following intravenous injection of KCN into mice. 4. E-2001 suppressed the high potassium-evoked release of glutamate from rat hippocampal slices. Furthermore, E-2001 prevented the excessive accumulation of extracellular glutamate induced by a brief ischemia in gerbils. 5. E-2001 exerted calcium antagonistic action, i.e., a relaxing effect on high potassium-induced contraction of rat aorta. 6. E-2001 exerted inhibitory action on the lipoperoxide production in vitro and in vivo, and exhibited a radical scavenging effect against O- and N-radicals. These results suggest that E-2001 might be effective as a novel anti-ischemic agent.

• Authors: T Kaneko, T Nakazawa, M Ueno, Y Furuya, M Ikeda, M Mihara, K Abe, K Tanaka, T Uzuo, T Fukuda
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 39 Issue 4 Pg. 445-50 (Apr 1989) ISSN: 0004-4172 [Print] Germany
• PMID: 2751730 (Publication Type: Journal Article)

Chemical References

• Cardiovascular Agents
• Free Radicals
• Glutamates
• Lipid Peroxides
• Naphthalenes
• Piperidines
• 2-(4-(4-fluorobenzoyl)piperidin-1-yl)-2'-acetonaphthone
• Potassium Cyanide
• Potassium

Topics

• Animals
• Brain Ischemia (drug therapy, metabolism, physiopathology)
• Cardiovascular Agents (pharmacology, toxicity)
• Female
• Free Radicals
• Gerbillinae
• Glutamates (metabolism)
• Hippocampus (blood supply, drug effects, metabolism)
• Ischemia (drug therapy, metabolism, physiopathology)
• Lipid Peroxides (metabolism)
• Male
• Mice
• Muscle Contraction (drug effects)
• Muscle, Smooth, Vascular (drug effects)
• Naphthalenes (pharmacology, toxicity)
• Neurons (drug effects)
• Piperidines (pharmacology, toxicity)
• Potassium (pharmacology)
• Potassium Cyanide (pharmacology)
• Rats