2008
DOI: 10.1007/s00702-008-0053-4
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MKC-231, a choline-uptake enhancer: (1) long-lasting cognitive improvement after repeated administration in AF64A-treated rats

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 detec… Show more

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Cited by 13 publications
(10 citation statements)
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“…In animal models of AD, i.e., β-amyloid protein-expressing transgenic and AF64A-injected mice, 25-30% decrease in brain ACh resulted in severe impairment of learning and memory function (Yamazaki et al, 1991;Abe et al, 1993;Tsai et al, 2007;Bessho et al, 2008). During aging, brain atrophy and malfunction of cholinergic nervous system occur, leading to cognitive defi cit.…”
Section: Discussionmentioning
confidence: 99%
“…In animal models of AD, i.e., β-amyloid protein-expressing transgenic and AF64A-injected mice, 25-30% decrease in brain ACh resulted in severe impairment of learning and memory function (Yamazaki et al, 1991;Abe et al, 1993;Tsai et al, 2007;Bessho et al, 2008). During aging, brain atrophy and malfunction of cholinergic nervous system occur, leading to cognitive defi cit.…”
Section: Discussionmentioning
confidence: 99%
“…The development of ASP-2535 (Astellas; a glycine transporter-1 inhibitor [280]), coluracetam (BCI-540, MKC-231; BrainCells Inc. under license from Mitsubishi Tanabe Pharma; an enhancer of high-affinity choline uptake and K + -induced release of acetylcholine [281][282][283][284][285][286][287][288]), CP-101 (CogniPharm, an i.v. formulation of modafinil), D-serine re-uptake inhibitors (Memory Pharmaceuticals, now Roche), flufenoxina (FAES Farma; a dual serotonin and norepinephrine re-uptake inhibitor), glycine transporter-1 inhibitors (Helicon Therapeutics), JNJ-17305600 (NFPS; NPS Allelix; a glycine transporter inhibitor [289]), PD-2007 (P2D Bioscience, a dopamine transporter inhibitor), SCH-900435 (Org-25935; Organon, Schering-Plough, now Merck, a glycine transporter-1 inhibitor), SSR-103800 [290][291][292]) and SSR-504734 (both sanofi; both glycine transporter-1 inhibitors [293][294][295][296][297]), teniloxazine (sufoxazine, Lucelan, Metatone, Y-8894, Yoshitomi, Mitsubishi Pharma, a noradrenaline uptake inhibitor [298], [299][300][301]), and tesofensine (NS-2330, NeuroSearch, a monoamine re-uptake inhibitors of serotonin, dopamine, and noradrenaline [302]) was terminated.…”
Section: Drugs Interacting With Re-uptake Transporters (Psychostimulants)mentioning
confidence: 99%
“…The infusion of AF64A into either the hippocampus or lateral ventricle induced defects of cholinergic nervous system, such as choline uptake, reduction of ChAT and AChE activities, reduction of ACh release and the destruction of the presynaptic terminals in cholinergic pathways (Fisher et al, 1982;Bessho et al, 2008). The AF64A-treated animals have been reported to have impaired motivation, learning and memory (Chrobak et al, 1988;Lim et al, 2001).…”
Section: Introductionmentioning
confidence: 97%