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Other names | TV-3326; (N-Propargyl-(3R)-aminoindan-5-yl)-N-propylcarbamate |
Routes of administration | Oral |
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Formula | C16H20N2O2 |
Molar mass | 272.348 g·mol−1 |
Ladostigil (developmental code name TV-3326) is a novel neuroprotective agent being investigated for the treatment of neurodegenerative disorders like Alzheimer's disease, Lewy body disease, and Parkinson's disease. [1] [2] It was developed from structural modification of rasagiline. [3]
The drug acts as a reversible acetylcholinesterase and butyrylcholinesterase inhibitor, and an irreversible monoamine oxidase B inhibitor, and combines the mechanisms of action of older drugs like rivastigmine and rasagiline into a single molecule. [4] [5] In addition to its neuroprotective properties, ladostigil enhances the expression of neurotrophic factors like GDNF and BDNF, and may be capable of reversing some of the damage seen in neurodegenerative diseases via the induction of neurogenesis. [6] Ladostigil also has antidepressant-like effects in animals, and may be useful for treating comorbid depression and anxiety often seen in such diseases as well. [7] [8]
There have been no new updates on the pharmaceutical development of ladostigil since 2019. [1] At this time, it was in phase 2 clinical trials for Alzheimer's disease. [1]
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.
Phenelzine, sold under the brand name Nardil, among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine family which is primarily used as an antidepressant and anxiolytic to treat depression and anxiety. Along with tranylcypromine and isocarboxazid, phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use.
Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively. It is also effective in the treatment of ADHD.
β-Carboline (9H-pyrido[3,4-b]indole) represents the basic chemical structure for more than one hundred alkaloids and synthetic compounds. The effects of these substances depend on their respective substituent. Natural β-carbolines primarily influence brain functions but can also exhibit antioxidant effects. Synthetically designed β-carboline derivatives have recently been shown to have neuroprotective, cognitive enhancing and anti-cancer properties.
Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl, Zelapar, and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It has also been studied for a variety of other indications, but has not been formally approved for any other use. The medication in the form licensed for depression has modest effectiveness for this condition that is similar to that of other antidepressants. Selegiline is provided as a swallowed tablet or capsule or an orally disintegrating tablet (ODT) for Parkinson's disease and as a patch applied to skin for depression.
Dopaminergic means "related to dopamine", dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.
Moclobemide, sold under the brand names Amira, Aurorix, Clobemix, Depnil and Manerix among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat depression and social anxiety. It is not approved for use in the United States, but is approved in other Western countries such as Canada, the UK and Australia. It is produced by affiliates of the Hoffmann–La Roche pharmaceutical company. Initially, Aurorix was also marketed by Roche in South Africa, but was withdrawn after its patent rights expired and Cipla Medpro's Depnil and Pharma Dynamic's Clorix became available at half the cost.
Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time, which can be expressed as a differential equation.
Rasagiline, sold under the brand name Azilect among others, is a medication which is used in the treatment of Parkinson's disease. It is used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases. The drug is taken by mouth.
In the management of Parkinson's disease, due to the chronic nature of Parkinson's disease (PD), a broad-based program is needed that includes patient and family education, support-group services, general wellness maintenance, exercise, and nutrition. At present, no cure for the disease is known, but medications or surgery can provide relief from the symptoms.
Tesofensine (NS2330) is a serotonin–noradrenaline–dopamine reuptake inhibitor from the phenyltropane family of drugs, which is being developed for the treatment of obesity. Tesofensine was originally developed by a Danish biotechnology company, NeuroSearch, who transferred the rights to Saniona in 2014.
CX-614 is an ampakine drug developed by Cortex Pharmaceuticals. It has been investigated for its effect on AMPA receptors.
Monoamine oxidase B, also known as MAO-B, is an enzyme that in humans is encoded by the MAOB gene.
LY-503430 is an AMPA receptor positive allosteric modulator developed by Eli Lilly.
Rivastigmine is a cholinesterase inhibitor used for the treatment of mild to moderate Alzheimer's disease. The drug can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which typically include nausea and vomiting.
Mofegiline (MDL-72,974) is a selective, irreversible inhibitor of monoamine oxidase B (MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) which was under investigation for the treatment of Parkinson's disease and Alzheimer's disease, but was never marketed.
Moussa B. H. Youdim is an Israeli neuroscientist specializing in neurochemistry and neuropharmacology. He is the discoverer of both monoamine oxidase (MAO) B inhibitors l-deprenyl (Selegiline) and rasagiline (Azilect) as anti-Parkinson drugs which possess neuroprotective activities. He is currently professor emeritus at Technion - Faculty of Medicine and President of Youdim Pharmaceuticals.
Epigenetics of depression is the study of how epigenetics contribute to depression.
Neurotrophin mimetics are small molecules or peptide like molecules that can modulate the action of the neurotrophin receptor. One of the main causes of neurodegeneration involves changes in the expression of neurotrophins (NTs) and/or their receptors. Indeed, these imbalances or changes in their activity, lead to neuronal damage resulting in neurological and neurodegenerative conditions. The therapeutic properties of neurotrophins attracted the focus of many researchers during the years, but the poor pharmacokinetic properties, such as reduced bioavailability and low metabolic stability, the hyperalgesia, the inability to penetrate the blood–brain barrier and the short half-lives render the large neurotrophin proteins not suitable to be implemented as drugs.
Desmethylselegiline (DMS), also known as norselegiline or as N-propargyl-L-amphetamine, is an active metabolite of selegiline, a medication used in the treatment of Parkinson's disease and depression.
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