MKC-231, a Choline-Uptake Enhancer: (1) Long-Lasting Cognitive Improvement After Repeated Administration in AF64A-treated Rats

J Neural Transm (Vienna). 2008 Jul;115(7):1019-25. doi: 10.1007/s00702-008-0053-4. Epub 2008 May 7.

Abstract

MKC-231 is reported to increase high-affinity choline uptake (HACU) in vitro and improve learning impairment on a single oral administration in AF64A-treated rats. In this study, we investigated the effects of repeated administration of MKC-231 (1 and 3 mg/kg, p.o., 8 days) on learning impairment in the water-maze task in AF64A-treated rats 1, 24, 48, and 72 h after the last dose. Significant cognitive improvement was observed for 24 h, however, concentration measurement studies indicated MKC-231 was not detected in the brain by this time. We also studied the effects of 8-days repeated administration of MKC-231 on HACU 1, 24, 48, and 72 h after the last dose and observed an increase of HACU similar in time course with cognitive improvement. From these results, we discussed the possibility that MKC-231 could induce long-lasting procognitive effects by changing the choline transporter regulation system.

MeSH terms

  • Animals
  • Aziridines*
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Carbon Isotopes / pharmacokinetics
  • Choline / analogs & derivatives*
  • Choline / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Interactions
  • Hippocampus / pathology
  • Hippocampus / ultrastructure
  • Learning Disabilities / chemically induced*
  • Learning Disabilities / drug therapy*
  • Learning Disabilities / pathology
  • Male
  • Maze Learning / drug effects
  • Quinolines / chemistry
  • Quinolines / pharmacokinetics
  • Quinolines / therapeutic use*
  • Rats
  • Rats, Wistar
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism
  • Time Factors

Substances

  • Aziridines
  • Carbon Isotopes
  • Quinolines
  • ethylcholine aziridinium
  • Choline
  • MKC 231