A novel cholinesterase and brain-selective monoamine oxidase inhibitor for the treatment of dementia comorbid with depression and Parkinson's disease

@article{Weinstock2003ANC,
  title={A novel cholinesterase and brain-selective monoamine oxidase inhibitor for the treatment of dementia comorbid with depression and Parkinson's disease},
  author={Marta Weinstock and Elena K. Gorodetsky and Tatyana Poltyrev and Aviva Gross and Yotam Sagi and Moussa B. H. Youdim},
  journal={Progress in Neuro-Psychopharmacology and Biological Psychiatry},
  year={2003},
  volume={27},
  pages={555-561}
}
The neurochemical and behavioral effects of the novel cholinesterase–monoamine oxidase inhibitor, ladostigil, in response to L‐dopa and L‐tryptophan, in rats
TLDR
The results suggest that potentiation of both aminergic and cholinergic transmission systems by ladostigil contributes equally to motor behavior performance, which is substantially impaired in comorbidity of dementia with Parkinsonism including dementia with Lewy bodies (DLB).
Role of Monoamine Oxidase Activity in Alzheimer’s Disease: An Insight into the Therapeutic Potential of Inhibitors
TLDR
There is a developing frame of proof indicating that monoamine oxidase-A (MAO-A) inhibitors may also play a role in neuroprotection, and the therapeutic potential of MAOIs alongside the complete understanding of the enzyme’s physiology may lead to the future advancement of these drugs.
Restoration of Nigrostriatal Dopamine Neurons in Post-MPTP Treatment by the Novel Multifunctional Brain-Permeable Iron Chelator-Monoamine Oxidase Inhibitor Drug, M30
TLDR
The findings suggest that brain-permeable M30 may clearly be of clinical importance for the treatment of PD.
MONOAMINE OXIDASE AND ITS INHIBITORS CORRELATING TO NEURODEGENERATIVE DISORDERS (REVIEW)
TLDR
The basic function of this enzyme is the modulation of brain neurotransmitters that are associated with numerous disorders such as neurodegenerative diseases including schizophrenia, anxiety, depression, migraine and sexual maturation.
CNS Targets for multi-functional drugs in the treatment of Alzheimer’s and Parkinson’s diseases
TLDR
New potential approaches in which molecules have been developed expressly to target multiple brain systems for the treatment of memory and cognition impairment in patients with mild forms of dementia and age-related memory impairment are summarized.
Monoamine oxidase inhibitors, and iron chelators in depressive illness and neurodegenerative diseases
  • M. Youdim
  • Biology
    Journal of Neural Transmission
  • 2018
TLDR
Recent novel therapeutic drugs for neurodegenerative diseases has led to the development of multi target drugs, that possess selective brain MAO A and B inhibitory moiety, iron chelating and antioxidant activities and the ability to increase brain levels of endogenous neurotrophins.
...
...

References

SHOWING 1-10 OF 60 REFERENCES
Effect of TV3326, a novel monoamine-oxidase cholinesterase inhibitor, in rat models of anxiety and depression
TLDR
TV3326 has potential antidepressant-like activity when given in a dose regimen that causes significant inhibition of brain MAO-A and -B and together with its neuroprotective properties could make TV3326 a potentially valuable drug for the treatment of dementia in patients with depression.
Selectivity of Cholinesterase Inhibition
TLDR
Eight cholinesterase inhibitors that reduce the inactivation of acetylcholine (ACh) have been tested in placebo-controlled trials in patients with Alzheimer’s disease and were found to improve cognitive function, or delay its rate of decline, in a significant proportion of patients.
TV3326, a novel neuroprotective drug with cholinesterase and monoamine oxidase inhibitory activities for the treatment of Alzheimer's disease.
TLDR
TV3326 and TV3279 protect against ischemia-induced cytotoxicity in PC12 cells and reduce the oedema, deficits in motor function and memory after closed head injury in mice and shows selectivity for brain MAO, even after 2 months of daily administration, with little or no effect on the enzyme in the intestinal tract and liver.
The monoamine oxidases of brain: selective inhibition with drugs and the consequences for the metabolism of the biogenic amines.
  • H. Y. Yang, N. Neff
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1974
TLDR
It is postulate that it may be possible to alter selectively the metabolism of the putative transmitter amines in man by administration of monoamine oxidase inhibitor drugs that preferentially inactivate a specific type of monoamines.
Neuroprotective Effects of Novel Cholinesterase Inhibitors Derived from Rasagiline as Potential Anti‐Alzheimer Drugs
TLDR
The study reported here examined the neuropotective effects of TV3326 against various insults in vitro and in vivo and found the neuroprotective effect in PC12 cells may be due to a combination of ChE inhibition and antiapoptotic activity.
The potentiation of the anti akinetic effect after L-Dopa treatment by an inhibitor of Mao-B, deprenil
TLDR
Deprenil is an inhibitor of MAO-B and is characterized by less frequent side effects, which can be eliminated by lowering the dosage of Deprenil, which is an excellent drug for preventing these.
Development of a novel neuroprotective drug (TV3326) for the treatment of Alzheimer's disease, with cholinesterase and monoamine oxidase inhibitory activities
TLDR
TV3326 significantly reduces hippocampal cell damage caused by global ischaemia in gerbils and the cerebral oedema induced by closed head injury in mice and speeds recovery of their motor and memory deficits and could clearly be of clinical importance for the treatment of Alzheimer's disease.
Selective Inhibitors of Butyrylcholinesterase
TLDR
It is postulated that two pools of ChEs may be present in the brain: one mainly neuronal and AChE dependent; and one mainly glial and BuE dependent and can be separated with selective inhibitors.
Brain metabolic and clinical effects of rivastigmine in Alzheimer's disease.
TLDR
Rivastigmine prevented the expected deterioration in clinical status and dramatically increased brain metabolic activity in a majority of patients, consistent with the literature suggesting that FDG-PET can sensitively measure the progression of AD and its improvement with cholinesterase inhibitors.
...
...