PMID- 8740080
DA - 19961016
DCOM- 19961016
LR - 20001218
IS - 0004-4172
VI - 46
IP - 4
DP - 1996 Apr
TI - 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.
PG - 369-73 AB - 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.
AD - Pharmaceuticals Laboratory 1, Yokohama Research Center, Mitsubishi
Chemical Corporation, Japan.
FAU - Bessho, T
AU - Bessho T
FAU - Takashina, K
AU - Takashina K
FAU - Tabata, R
AU - Tabata R
FAU - Ohshima, C
AU - Ohshima C
FAU - Chaki, H
AU - Chaki H
FAU - Yamabe, H
AU - Yamabe H
FAU - Egawa, M
AU - Egawa M
FAU - Tobe, A
AU - Tobe A
FAU - Saito, K
AU - Saito K
LA - eng
PT - Journal Article
CY - GERMANY
TA - Arzneimittelforschung
JID - 0372660
RN - 0 (Aziridines)
RN - 0 (MKC 231)
RN - 0 (Neuromuscular Blocking Agents)
RN - 0 (Nootropic Agents)
RN - 0 (Quinolines)
RN - 0 (Receptors, Muscarinic)
RN - 321-64-2 (Tacrine)
RN - 62-49-7 (Choline)
RN - 63918-37-6 (ethylcholine aziridinium)
RN - EC 3.1.1.7 (Acetylcholinesterase)
SB - IM
MH - Acetylcholinesterase/metabolism
MH - Animal
MH - Aziridines/pharmacology
MH - Body Temperature/drug effects
MH - Choline/analogs & derivatives/*metabolism/pharmacology
MH - Comparative Study
MH - Hippocampus/drug effects/metabolism
MH - In Vitro
MH - Male
MH - Maze Learning/*drug effects
MH - Neuromuscular Blocking Agents/pharmacology
MH - Nootropic Agents/*pharmacology
MH - Quinolines/*pharmacology
MH - Rats
MH - Rats, Wistar
MH - Receptors, Muscarinic/drug effects/metabolism
MH - Salivation/drug effects
MH - Tacrine/pharmacology
MH - Tremor/chemically induced
EDAT- 1996/04/01
MHDA- 1996/04/01 00:01
PST - ppublish
SO - Arzneimittelforschung 1996 Apr;46(4):369-73.