生物活性

• 描述Galanthamine is selective for acetylcholinesterase versus butyrylcholinesterase. Galanthamine attenuates drug-and lesion-induced cognitive deficits in animal models of learning and memory^[1]. Galanthamine acts as a positive allosteric modulator (PAM) of human α4β2 AChRs (accessory subunits in heteromeric nicotinic receptors) expressed in permanently transfected HEK 293 cells. Galanthamine increases the response of (α4β2)2α5 AChRs to 1 μM ACh by up to 220% with very low concerntration(EC50=0.25 nM). Only small potentiation (20%) of either α4β2 or (α4β2)2β3 AChRs is detected using FLEXstation assays. Galanthamine at concentrations of 1 μM and above inhibits all three AChR subtypes^[2]. Acute administration of galantamine (0.3-3 mg/kg, i.p.) increased IGF2 mRNA levels in the hippocampus, but not in the prefrontal cortex, in time- and dose-dependent manner. Galantamine (3 mg/kg, i.p.) caused a transient increase in fibroblast growth factor 2 mRNA levels and a decrease in brain-derived neurotrophic factor mRNA levels in the hippocampus, while it did not affect the mRNA levels of other neurotrophic/growth factors^[3]. Galantamine treatment prevented LPS-induced (lipopolysaccharide) deficits in spatial learning and memory as well as memory acquisition of the passive avoidance response. Galantamine reduced the inflammatory response not only in the BV-2 microglia cell line, but also in the HT-22 hippocampal neuronal cell line^[4].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02703636	Mild to Moderate Alzheimer's D... more >>isease Collapse <<	Phase 4	Completed	-	Japan ... more >> Novartis Investigative Site Fukuoka-city, Fukuoka, Japan, 814-001 Novartis Investigative Site Fukuoka-city, Fukuoka, Japan, 814-0180 Novartis Investigative Site Aizuwakamatsu, Fukushima, Japan, 965-8585 Novartis Investigative Site Tsukuba-city, Ibaraki, Japan, 305-8576 Novartis Investigative Site Kita-gun, Kagawa, Japan, 761-0793 Novartis Investigative Site Sagamihara-city, Kanagawa, Japan, 252-5188 Novartis Investigative Site Kochi-city, Kochi, Japan, 780-0842 Novartis Investigative Site Kurashiki-city, Okayama, Japan, 710-0826 Novartis Investigative Site Osaka-city, Osaka, Japan, 543-8555 Novartis Investigative Site Suita-city, Osaka, Japan, 565 0871 Novartis Investigative Site Kasukabe-city, Saitama, Japan, 344-0036 Novartis Investigative Site Koshigaya-city, Saitama, Japan, 343-0032 Novartis Investigative Site Fuji-city, Shizuoka, Japan Novartis Investigative Site Bunkyo-ku, Tokyo, Japan, 113-8431 Novartis Investigative Site Hachioji-city, Tokyo, Japan, 193-0944 Novartis Investigative Site Shinjuku-ku, Tokyo, Japan, 160-0023 Novartis Investigative Site Niigata, Japan Novartis Investigative Site Okayama, Japan, 710-0813 Novartis Investigative Site Tokyo, Japan, 168-8535 Collapse <<
  NCT00234637	Alzheimer's Disease	Phase 4	Completed	-	France ... more >> Département de Gérontologie Clinique Limoges, Cedex, France, 87042 Collapse <<
  NCT01529619	Alzheimer's Disease	Phase 4	Completed	-	Japan ... more >> Novartis Investigative Site Nagoya-city, Aichi, Japan, 467-8602 Novartis Investigative Site Fukuoka-city, Fukuoka, Japan, 814-0180 Novartis Investigative Site Miyoshi-city, Hiroshima, Japan, 728-0013 Novartis Investigative Site Ohtake, Hiroshima, Japan, 739-0696 Novartis Investigative Site Kita-gun, Kagawa, Japan, 761-0793 Novartis Investigative Site Kamakura-city, Kanagawa, Japan, 247-8533 Novartis Investigative Site Kawasaki-city, Kanagawa, Japan, 216-8511 Novartis Investigative Site Yokohama, Kanagawa, Japan, 241-0811 Novartis Investigative Site Koshi-city, Kumamoto, Japan, 861-1116 Novartis Investigative Site Kyoto-city, Kyoto, Japan, 600-8558 Novartis Investigative Site Kyoto, Japan, 606-0851 Collapse <<

• 更多
• 参考文献

• [1] Fulton B, Benfield P. Galanthamine. Drugs Aging. 1996 Jul;9(1):60-5; discussion 66-7

  [2] Kuryatov A, Onksen J, Lindstrom J. Roles of accessory subunits in alpha4beta2(*) nicotinic receptors. Mol Pharmacol. 2008 Jul;74(1):132-43

  [3] Kita Y, Ago Y, Takano E, Fukada A, Takuma K, Matsuda T. Galantamine increases hippocampal insulin-like growth factor 2 expression via α7 nicotinic acetylcholine receptors in mice. Psychopharmacology (Berl). 2013 Feb;225(3):543-51

  [4] Liu Y, Zhang Y, Zheng X, Fang T, Yang X, Luo X, Guo A, Newell KA, Huang XF, Yu Y. Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice. J Neuroinflammation. 2018 Apr 18;15(1):112