Effect of TV3326, a novel monoamine-oxidase cholinesterase inhibitor, in rat models of anxiety and depression

@article{Weinstock2002EffectOT,
  title={Effect of TV3326, a novel monoamine-oxidase cholinesterase inhibitor, in rat models of anxiety and depression},
  author={Marta Weinstock and Tatyana Poltyrev and Corina Bejar and Moussa B. H. Youdim},
  journal={Psychopharmacology},
  year={2002},
  volume={160},
  pages={318-324}
}
Abstract.Rationale: A high incidence of depression is found in subjects with Alzheimer's disease (AD), in whom many antidepressants are contraindicated because they have anticholinergic activity. We have designed a new cholinesterase inhibitor TV3326 [(N-propargyl-(3R) aminoindan-5-yl)-ethyl methyl carbamate] for the treatment of AD, which has neuroprotective activities and also blocks monoamine oxidase (MAO) A and B in the brain but not in the intestine after chronic administration. Objectives… 
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References

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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.
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.
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.
The Anti‐Parkinson Drug Rasagiline and Its Cholinesterase Inhibitor Derivatives Exert Neuroprotection Unrelated to MAO Inhibition in Cell Culture and in Vivo
TLDR
Neither TVP1022 nor TV3219 are MAO inhibitors, both share the antiapoptotic and neuroprotective actions of rasagiline, indicating that MAO inhibition is not a prerequisite for neuroprotection and that the propargyl moiety exhibits intrinsic neuroProtective pharmacological activity that requires identification.
Effects of moclobemide, a new generation reversible Mao-A inhibitor, in a novel animal model of depression.
TLDR
Results reinforce the value of this animal model with respect to its predictive and construct validity and suggest a gradual decrease in the rewarding properties of brain stimulation.
TV3326, A Novel Cholinesterase and Mao Inhibitor
TLDR
In order to delay the rate of progression of the neurodegeneration and ameliorate the cognitive deficits and depressive symptoms, a new drug, TV3326, is designed, derived from rasagiline, a selective monoamine oxidase (MAO)-B inhibitor (Youdim et al. 2001).
EFFECTS OF MONOAMINE OXIDASE INHIBITION BY CLORGYLINE, DEPRENIL OR TRANYLCYPROMINE ON 5‐HYDROXYTRYPTAMINE CONCENTRATIONS IN RAT BRAIN AND HYPERACTIVITY FOLLOWING SUBSEQUENT TRYPTOPHAN ADMINISTRATION
TLDR
It is concluded that while 5‐HT may normally be metabolized in the brain by ‘Type A’ MAO in vivo, when this form is inhibited,5‐HT can still be metabolitesized by ’Type B’ enzyme.
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