生物活性

• 描述Galanthamine hydrobromide is a selective, reversible, competitive, alkaloid AChE (acetylcholinesterase) inhibitor, with an IC50 of 0.35 µM. Galanthamine hydrobromide is a potent allosteric potentiating ligand (APL) of human α3β4, α4β2, α6β4 nicotinic receptors (nAChRs). Galanthamine hydrobromide is 53-fold selectivity for AChE over butyrylcholinesterase^[3]. Galanthamine hydrobromide (25-1000 µM) inhibits both Aβ 1-40 (50 µM) and Aβ 1-42 (50 µM) aggregation. Galanthamine hydrobromide (25-1000 µM) protects against Aβ(1-40) and Aβ(1-42) toxicity in SH-SY5Y cells. Galanthamine hydrobromide also dramatically reduces Aβ(1-40)-induced cellular apoptosis^[4]. Galanthamine hydrobromide (1.25-2.5 mg/kg; i.p.) reduces cognitive deficits in APP23 mice^[5]. Galantamine treatment prevented LPS-induced deficits in spatial learning and memory as well as memory acquisition of the passive avoidance response. Galantamine decreased the expression of microglia and astrocyte markers (CD11b and GFAP), pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), and NF-κB p65 in the hippocampus of LPS-exposed mice. Furthermore, galantamine ameliorated LPS-induced loss of synapse-associated proteins (SYN and PSD-95) in the hippocampus. Importantly, galantamine reduced the inflammatory response not only in the BV-2 microglia cell line, but also in the HT-22 hippocampal neuronal cell line^[6].
• 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
  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 <<
  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 <<

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• 参考文献

• [1] Schultz BR, Takeshita J, et al. Simultaneous usage of dementia medications and anticholinergics among Asians and Pacific Islanders. Psychogeriatrics. 2017 Apr 7.

  [2] Petersen RC, Thomas RG, et al. Alzheimer's Disease Neuroimaging Initiative (ADNI) and Foundation for NIH (FNIH) Biomarkers Consortium AD MCI Placebo Data Analysis Project Team.. Randomized controlled trials in mild cognitive impairment: Sources of variability. Neurology. 2017 Apr 5. pii: 10.1212/WNL.0000000000003907.

  [3] Samochocki M, Höffle A, Fehrenbacher A, Jostock R, Ludwig J, Christner C, Radina M, Zerlin M, Ullmer C, Pereira EF, Lübbert H, Albuquerque EX, Maelicke A. Galantamine is an allosterically potentiating ligand of neuronal nicotinic but not of muscarinic acetylcholine receptors. J Pharmacol Exp Ther. 2003 Jun;305(3):1024-36

  [4] Matharu B, Gibson G, Parsons R, Huckerby TN, Moore SA, Cooper LJ, Millichamp R, Allsop D, Austen B. Galantamine inhibits beta-amyloid aggregation and cytotoxicity. J Neurol Sci. 2009 May 15;280(1-2):49-58

  [5] Van Dam D, Abramowski D, Staufenbiel M, De Deyn PP. Symptomatic effect of donepezil, rivastigmine, galantamine and memantine on cognitive deficits in the APP23 model. Psychopharmacology (Berl). 2005 Jun;180(1):177-90

  [6] 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

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