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

Arzneimittelforschung. 1996 Apr;46(4):369-73.

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.

Publication types

  • Comparative Study

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Aziridines / pharmacology
  • Body Temperature / drug effects
  • Choline / analogs & derivatives
  • Choline / metabolism*
  • Choline / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / 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
  • Receptors, Muscarinic / metabolism
  • Salivation / drug effects
  • Tacrine / pharmacology
  • Tremor / chemically induced

Substances

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