"目录号: HY-14537
PI3K/Akt/mTOREpigeneticsAutophagy-
Latrepirdine是一个强的AMPK激活剂，也是抗组胺，能够促进α-synuclein蛋白聚合的移动。
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生物活性
Description
Latrepirdine (dihydrochloride) is a potent activator of AMPK, also an anti-histamine, promote the removal of α-synuclein protein aggregates. target: AMPKIn vitro: Latrepirdine is shown to up-regulate yeast vacuolar (lysosomal) activity and promote transport of the autophagic marker (Atg8) to the vacuole. Latrepirdine treatment attenuat Aβ42-induced toxicity in wild-type cells but not in the Atg8Δ mutant.[1] In line with a stabilizing effect of latrepirdine on plasma membrane potential, pretreatment with latrepirdine reduced spontaneous Ca2+ oscillations as well as glutamate-induced Ca2+ increases in primary neurons, and protected neurons against glutamate toxicity. Latrepirdine also increased mitochondrial uptake of the voltage-sensitive probe TMRM. [2]In vivo: Treatment with latrepirdine increase AMPK activity in primary mouse motor neuroncultures and in SOD1G93A lumbar spinal cords. Mice "preconditioned" with latrepirdine show a delayed symptom onset and a significant increase in life span. (1 μg/kg, intraperitoneal ).[3]
Clinical Trial
Medivation, Inc.-Huntington Study Group
Huntington's Disease
July 2007
Phase 2
Medivation, Inc.-Pfizer
Huntington Disease
July 2009
Phase 3
Medivation, Inc.
Alzheimer's Disease
December 2008
Phase 1
Medivation, Inc.
Alzheimer's Disease
September 2005
Phase 2
Medivation, Inc.
Alzheimer's Disease
May 2008
Phase 3
Medivation, Inc.
Alzheimer's Disease
April 2008
Phase 2
Pfizer-Medivation, Inc.
Alzheimer Disease
September 2009
Phase 3
Pfizer-Medivation, Inc.
Alzheimer's Disease
September 2009
Phase 3
Medivation, Inc.-Huntington Study Group
Huntington's Disease
October 2006
Phase 1-Phase 2
Pfizer-Medivation, Inc.
Alzheimer's Disease-Huntington's Disease
February 2009
Phase 1
Medivation, Inc.-Pfizer
Huntington Disease
February 2010
Phase 3
Pfizer-Medivation, Inc.
Alzheimer's Disease-Huntington's Disease
July 2009
Phase 1
Pfizer-Medivation, Inc.
Alzheimer's Disease-Huntington's Disease
February 2009
Phase 1
Pfizer-Medivation, Inc.
Alzheimer's Disease-Huntington's Disease
October 2009
Phase 1
Pfizer-Medivation, Inc.
Alzheimer Disease-Huntington Disease
February 2009
Phase 1
Pfizer-Medivation, Inc.
Huntington Disease-Alzheimer Disease
November 2008
Phase 1
Pfizer-Medivation, Inc.
Hepatic Failure
February 2009
Phase 1
Pfizer-Medivation, Inc.
Alzheimer's Disease
April 2010
Phase 3
Pfizer-Medivation, Inc.
Alzheimer's Disease-Huntington's Disease
February 2009
Phase 1
Medivation, Inc.-Pfizer
Moderate to Severe Alzheimer
October 2009
Phase 3
Pfizer-Medivation, Inc.
Healthy Volunteers
June 2009
Phase 1
Pfizer-Medivation, Inc.
Alzheimer's Disease-Huntington Disease
October 2009
Phase 1
Pfizer-Medivation, Inc.
Alzheimer's Disease
February 2009
Phase 3
Medivation, Inc.-Pfizer
Alzheimer's Disease
March 2009
Phase 3
Medivation, Inc.-Pfizer
Alzheimer's Disease
April 2010
Phase 3
Pfizer-Medivation, Inc.
Alzheimer's Disease-Huntington's Disease
October 2009
Phase 1
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References
