MKC-231, a choline-uptake enhancer: (1) long-lasting cognitive improvement after repeated administration in AF64A-treated rats.
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.
Bessho
Tomoko
T
Pharmacology Department IV, Pharmacology Laboratory, Research Division, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. Bessho.Tomoko@mf.mt-pharma.co.jp
Takashina
Ken
K
Eguchi
Junichi
J
Komatsu
Teiko
T
Saito
Ken-Ichi
K
D000818:Animals; D001388:Aziridines; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D006624:Hippocampus / Q000473:pathology / Q000648:ultrastructure; D007859:Learning Disabilities / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D011804:Quinolines / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D001388:Aziridines; D002247:Carbon Isotopes; D011804:Quinolines; C044894:ethylcholine aziridinium; D002794:Choline; C092988:MKC 231