Effect of the novel high affinity choline uptake enhancer 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b] quinolin-4-yl)acetoamide on deficits of water maze learning in rats.

Abstract

The pharmacological properties of MKC-231 (2-(2-oxopyrrolidin-1-yl)-N- (2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl) acetoamide, CAS 135463-81-9) in comparison with an acetylcholinesterase (AChE) inhibitor, tacrine (CAS 1684-40-8) were studied. MKC-231(10(-10)-10(-6) moll) significantly increased high affinity choline uptake (HACU) when it was incubated with the hippocampal synaptosomes of ethylcholine mustard aziridinium ion (AF64A) treated rats, but not of normal rats. MKC-231 did not affect the AChE activity, [3H]- quinuclidinyl benzilate binding, and [3H]-pirenzepine binding. Oral administration of MKC-231 (1-10 mg/kg) significantly improved the learning deficits in the Morris' water maze of AF64A-treated rats, but it did not produce any significant side effects, like tremor, salivation or hypothermia, which were observed in rats treated with high doses of tacrine. Tacrine (0.1-3 mg/kg p.o.) failed to ameliorate the learning deficits in AF64A-treated rats. These results suggest that MKC-231 is a novel and quite unique compound, which improves the memory impairment induced by AF64A through the enhancement of HACU without any side effects at the effective doses.

• Authors: T Bessho, K Takashina, R Tabata, C Ohshima, H Chaki, H Yamabe, M Egawa, A Tobe, K Saito
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 46 Issue 4 Pg. 369-73 (Apr 1996) ISSN: 0004-4172 [Print] Germany
• PMID: 8740080 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Aziridines
• Neuromuscular Blocking Agents
• Nootropic Agents
• Quinolines
• Receptors, Muscarinic
• Tacrine
• ethylcholine aziridinium
• Acetylcholinesterase
• Choline
• MKC 231

Topics

• Acetylcholinesterase (metabolism)
• Animals
• Aziridines (pharmacology)
• Body Temperature (drug effects)
• Choline (analogs & derivatives, metabolism, pharmacology)
• Hippocampus (drug effects, metabolism)
• In Vitro Techniques
• Male
• Maze Learning (drug effects)
• Neuromuscular Blocking Agents (pharmacology)
• Nootropic Agents (pharmacology)
• Quinolines (pharmacology)
• Rats
• Rats, Wistar
• Receptors, Muscarinic (drug effects, metabolism)
• Salivation (drug effects)
• Tacrine (pharmacology)
• Tremor (chemically induced)