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Journal of Neural Transmission

, Volume 115, Issue 7, pp 1019–1025 | Cite as

MKC-231, a choline-uptake enhancer: (1) long-lasting cognitive improvement after repeated administration in AF64A-treated rats

  • Tomoko BesshoEmail author
  • Ken Takashina
  • Junichi Eguchi
  • Teiko Komatsu
  • Ken-Ichi Saito
Alzheimer's Disease and Related Disorders - Original Article

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.

Keywords

MKC-231 AF64A High-affinity choline uptake (HACU) Water-maze 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Tomoko Bessho
    • 1
    Email author
  • Ken Takashina
    • 1
  • Junichi Eguchi
    • 1
  • Teiko Komatsu
    • 2
  • Ken-Ichi Saito
    • 3
  1. 1.Pharmacology Department IV, Pharmacology Laboratory, Research DivisionMitsubishi Tanabe Pharma CorporationYokohamaJapan
  2. 2.Development Regulatory Affairs Department, Development DivisionMitsubishi Tanabe Pharma CorporationTokyoJapan
  3. 3.Global Product Strategy DepartmentMitsubishi Tanabe Pharma CorporationTokyoJapan

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