Latrepirdine dihydrochloride

"目錄號: HY-14537

PI3K/Akt/mTOREpigeneticsAutophagy-

Latrepirdine是一個強的AMPK激活劑汁讼,也是抗組胺,能夠促進α-synuclein蛋白聚合的移動阔墩。

AMPKAutophagy

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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

NCT00497159

Medivation, Inc.-Huntington Study Group

Huntington's Disease

July 2007

Phase 2

NCT00920946

Medivation, Inc.-Pfizer

Huntington Disease

July 2009

Phase 3

NCT00829816

Medivation, Inc.

Alzheimer's Disease

December 2008

Phase 1

NCT00377715

Medivation, Inc.

Alzheimer's Disease

September 2005

Phase 2

NCT00675623

Medivation, Inc.

Alzheimer's Disease

May 2008

Phase 3

NCT00704782

Medivation, Inc.

Alzheimer's Disease

April 2008

Phase 2

NCT00912288

Pfizer-Medivation, Inc.

Alzheimer Disease

September 2009

Phase 3

NCT00939783

Pfizer-Medivation, Inc.

Alzheimer's Disease

September 2009

Phase 3

NCT00387270

Medivation, Inc.-Huntington Study Group

Huntington's Disease

October 2006

Phase 1-Phase 2

NCT00827034

Pfizer-Medivation, Inc.

Alzheimer's Disease-Huntington's Disease

February 2009

Phase 1

NCT01085266

Medivation, Inc.-Pfizer

Huntington Disease

February 2010

Phase 3

NCT00931073

Pfizer-Medivation, Inc.

Alzheimer's Disease-Huntington's Disease

July 2009

Phase 1

NCT00824590

Pfizer-Medivation, Inc.

Alzheimer's Disease-Huntington's Disease

February 2009

Phase 1

NCT00990613

Pfizer-Medivation, Inc.

Alzheimer's Disease-Huntington's Disease

October 2009

Phase 1

NCT00831506

Pfizer-Medivation, Inc.

Alzheimer Disease-Huntington Disease

February 2009

Phase 1

NCT00788047

Pfizer-Medivation, Inc.

Huntington Disease-Alzheimer Disease

November 2008

Phase 1

NCT00831532

Pfizer-Medivation, Inc.

Hepatic Failure

February 2009

Phase 1

NCT01066546

Pfizer-Medivation, Inc.

Alzheimer's Disease

April 2010

Phase 3

NCT00825084

Pfizer-Medivation, Inc.

Alzheimer's Disease-Huntington's Disease

February 2009

Phase 1

NCT00954590

Medivation, Inc.-Pfizer

Moderate to Severe Alzheimer

October 2009

Phase 3

NCT00907322

Pfizer-Medivation, Inc.

Healthy Volunteers

June 2009

Phase 1

NCT00988624

Pfizer-Medivation, Inc.

Alzheimer's Disease-Huntington Disease

October 2009

Phase 1

NCT00838110

Pfizer-Medivation, Inc.

Alzheimer's Disease

February 2009

Phase 3

NCT00829374

Medivation, Inc.-Pfizer

Alzheimer's Disease

March 2009

Phase 3

NCT01152216

Medivation, Inc.-Pfizer

Alzheimer's Disease

April 2010

Phase 3

NCT00975481

Pfizer-Medivation, Inc.

Alzheimer's Disease-Huntington's Disease

October 2009

Phase 1

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References

[1].Bharadwaj PR et al. Latrepirdine (dimebon) enhances autophagy and reduces intracellular GFP-Aβ42 levels in yeast. J Alzheimers Dis. 2012;32(4):949-67.

[2].Weisová P et al. Latrepirdine is a potent activator of AMP-activated protein kinase and reduces neuronal excitability.

[3].Coughlan KS et al. "Preconditioning" with latrepirdine, an adenosine 5'-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1(G93A) mice. Neurobiol Aging. 2015 Feb;36(2):1140-50.

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