![]() | A major contributor to this article appears to have a close connection with its subject.(April 2018) |
Moussa B. H. Youdim | |
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![]() Moussa B.H. Youdim | |
Born | 1935 |
Nationality | Israeli |
Known for | Development of anti-Parkinson drugs (selegiline and rasagiline) |
Awards |
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Scientific career | |
Fields | Neuroscience, Neuropharmacology |
Institutions |
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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.
Youdim was born in Tehran, Iran second of five children. His father worked and traded with the British and wanted that the boys to be educated in England. He and his brother were sent to England boarding school in UK. He had an ambition to go to medical school to study medicine and obtained his preclinical studies in Borough Polytechnique in London. he was accepted at McGill University in Montreal where he aobtained his B.Sc. degree. A lecture in neurochemsitry changed his mind about medical degree and decided to study brain chemistry.
Youdim upon joining Professor Theodore L Sourkes's laboratory at Allan Memorial Institute, McGill Department of Psychiatry, he began to work on the M.Sc. focusing on characteristics of the enzume monoamine oixdase (MAO), followed by Ph.D. He has focused most of his life on the field of neurochemistry and neuropharmacology of aminergic neurotransmitters in health and disease. In his M.Sc. and Ph.D. Studies he purified mitochondrial MAO and demonstrated two forms of the enzymes, which were later named A and B by Johnson ( 1968). One of his most important contributions to science was working with Professor Merton Sandler in London University Post Graduate School to study MAO inhibitors as anti-depressants and anti-Parkinson drugs. While at Oxford University Medical School, a chance meeting with Professor Peter Riederer resulted in employing the MAO-B inhibitor, l-deprenyl (Later named selegiline) a failed anti depressant, in Parkinson's disease, since the human brain basal ganglia were rich in MAO-B and dopamine. The clinical study was a success and was confirmed by others in clinical studies and eventual approval of selegiline by FDA.
At Technion in Haifa he discovered the second MAO B inhibitor, AGN1135, which was 20 times more potent than selegiline. Together with Prof. John Finberg and Teva Pharmecueitacl AGN1135 was developed as an anti Parkinson's Disease drug called rasagiline (Azilect), approved by FDA in 2006. This drug had neuroprotective activity in cell culture and in vivo animal models of Parkinson's disease and may have disease modifying activity in Parkinson's disease.
He pioneered the study of brain iron dysregulation on brain function. This included its nutritional deficiency, which results in cognitive impairment and learning process in animal models and children with nutritional iron deficiency. And iron accumulation in brain neurons that degenerate resulting in Parkinson's and Alzheimer's diseases and ALS (amyotropic lateral sclerosis), where iron initiated oxidative stress may induce the process neurodegeneration. He was the first to demonstrate that iron chelators su desferal and VK-28 were neuroprotective in animal models of Parkinson's disease since neurodegeneration of substantia nigra dopamine neuros results in accumulation of iron. Free iron may cause generation of free radicals and oxidative stress. His other pioneering contribution is the development of multi-target drugs for treatment of Parkinson's and Alzheimer's diseases possessing iron chleating, monomaine oxidase and cholinesterase inhibitory activities
Youdim has published almost nine hundred papers and reviews and edited 45 books in neurochemistry, neuropharmacology, multi-target drug development, and transcriptomics.
Youdim served as consultant to Roche, TEVA Pharmaceuticals Ltd; Ciba Geigy, and Continental Pharmaceuticals, Brussels. He is president and CSO of Youdim Pharmaceutical. He is a discoverer of the anti-Parkinson drugs selelgiline (l-deprenyl) and developer of monoamine oxidase B inhibitor rasagiline (Azilect), which was considered to be the first disease modifying drug used for Parkinson's disease and TVP 3326, ladostigil, for Alzheimer's disease. [2] [3] Experts have recently questioned whether rasagiline actually has significant disease modifying properties. [4]
On the editorial boards of 40 journals, including British Journal of Pharmacology , Journal of Neurochemistry , Journal of Neural Transmission , Experimental Neurology , International Neurochemistry, Psychopharmacology. International Journal of Neuropsychopharmacology , Archives of Pharmacology, Frontiers in Pharmacology , European Journal of Pharmacology , Biogenic Amines, Neuropsychobiology , Neurochemical Research ; Brain Research , CNS Drug Review , Future Drugs, Drugs of Today, and Neurotherapeutics .
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.
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.
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.
Deprenyl, also known by its developmental code name E-250 and as N-propargylmethamphetamine, is the racemic mixture of D-deprenyl and L-deprenyl (selegiline). It was discovered in 1961 in Hungary at Chinoin Pharmaceutical Company by Zoltan Ecseri and Joseph Knoll, was patented in 1962, and was first described in the literature in 1964 or 1965.
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.
Omigapil is a drug that was developed by Novartis and tested in clinical trials for its ability to help treat Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). The development for PD and ALS have been terminated due to lack of benefit, but Santhera Pharmaceuticals bought the compound for development for the treatment of congenital muscular dystrophy (CMD).
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.
Pargyline, sold under the brand name Eutonyl among others, is a monoamine oxidase inhibitor (MAOI) medication which has been used to treat hypertension but is no longer marketed. It has also been studied as an antidepressant, but was never licensed for use in the treatment of depression. The drug is taken by mouth.
(–)-Benzofuranylpropylaminopentane is an experimental drug related to selegiline which acts as a monoaminergic activity enhancer (MAE). It is orally active in animals.
1-Phenyl-2-propylaminopentane is an experimental drug related to selegiline which acts as a catecholaminergic activity enhancer (CAE).
Monoamine oxidase B, also known as MAO-B, is an enzyme that in humans is encoded by the MAOB gene.
Levoamphetamine is a stimulant medication which is used in the treatment of certain medical conditions. It was previously marketed by itself under the brand name Cydril, but is now available only in combination with dextroamphetamine in varying ratios under brand names like Adderall and Evekeo. The drug is known to increase wakefulness and concentration in association with decreased appetite and fatigue. Pharmaceuticals that contain levoamphetamine are currently indicated and prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), obesity, and narcolepsy in some countries. Levoamphetamine is taken by mouth.
Carbidopa/levodopa/entacapone, sold under the brand name Stalevo among others, is a dopaminergic fixed-dose combination medication that contains carbidopa, levodopa, and entacapone for the treatment of Parkinson's disease.
Safinamide is a drug used as an add-on treatment for Parkinson's disease with "off" episodes; it has multiple modes of action, including the inhibition of monoamine oxidase B.
Ladostigil (TV-3,326) is a novel neuroprotective agent being investigated for the treatment of neurodegenerative disorders like Alzheimer's disease, Lewy body disease, and Parkinson's disease. It 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. 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. Ladostigil also has antidepressant effects, and may be useful for treating comorbid depression and anxiety often seen in such diseases as well.
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.
Opicapone, sold under the brand name Ongentys, is a medication which is administered together with levodopa in people with Parkinson's disease. Opicapone is a catechol-O-methyltransferase (COMT) inhibitor.
Monoaminergic activity enhancers (MAE), also known as catecholaminergic/serotonergic activity enhancers (CAE/SAE), are a class of compounds that enhance the action potential-evoked release of monoamine neurotransmitters in the nervous system. MAEs are distinct from monoamine releasing agents (MRAs) like amphetamine and fenfluramine in that they do not induce the release of monoamines from synaptic vesicles but rather potentiate only nerve impulse propagation-mediated monoamine release. That is, MAEs increase the amounts of monoamine neurotransmitters released by neurons per electrical impulse.
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.