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Dopamine is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% of the catecholamine content in the brain. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical, L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons to send signals to other nerve cells. Neurotransmitters are synthesized in specific regions of the brain, but affect many regions systemically. The brain includes several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain, and many addictive drugs increase dopamine release or block its reuptake into neurons following release. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones. These pathways and cell groups form a dopamine system which is neuromodulatory.
l-DOPA, also known as levodopa and l-3,4-dihydroxyphenylalanine, is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize l-DOPA, make it via biosynthesis from the amino acid l-tyrosine. l-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), which are collectively known as catecholamines. Furthermore, l-DOPA itself mediates neurotrophic factor release by the brain and CNS. In some plant families, l-DOPA is the central precursor of a biosynthetic pathway that produces a class of pigments called betalains. l-DOPA can be manufactured and in its pure form is sold as a psychoactive drug with the INN levodopa; trade names include Sinemet, Pharmacopa, Atamet, and Stalevo. As a drug, it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia.
Neuropharmacology is the study of how drugs affect function in the nervous system, and the neural mechanisms through which they influence behavior. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmacology focuses on the study of how drugs affect human behavior (neuropsychopharmacology), including the study of how drug dependence and addiction affect the human brain. Molecular neuropharmacology involves the study of neurons and their neurochemical interactions, with the overall goal of developing drugs that have beneficial effects on neurological function. Both of these fields are closely connected, since both are concerned with the interactions of neurotransmitters, neuropeptides, neurohormones, neuromodulators, enzymes, second messengers, co-transporters, ion channels, and receptor proteins in the central and peripheral nervous systems. Studying these interactions, researchers are developing drugs to treat many different neurological disorders, including pain, neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, psychological disorders, addiction, and many others.
Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a symptom of Parkinson's disease shown as muscle rigidity and an inability to produce movement. It is also associated with mental health disorders and prolonged inactivity due to illness, amongst other diseases.
A dopamine agonist(DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D1-like and D2-like. They are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. Dopamine agonists are primarily used in the treatment of the motor symptoms of Parkinson's disease, and to a lesser extent, in hyperprolactinemia and restless legs syndrome. They are also used off-label in the treatment of clinical depression. Impulse control disorders are associated with the use of dopamine agonists for whatever condition.
Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include: altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfiguring synaptic connectivity.
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.
Biotie Therapies was a Finnish biotechnology and pharmaceutics company that was acquired by Acorda Therapeutics in January 2016. The company's research and development was focused on drugs for neurodegenerative and psychiatric disorders like Parkinson's disease, Alzheimer's disease and other cognitive disorders, alcohol and drug dependence and post traumatic stress disorder, and inflammatory and fibrotic liver disease. The company's headquarters is in Turku, Western Finland, and it is listed on NASDAQ OMX Helsinki.
Quark Pharmaceuticals is a pharmaceutical company that develops RNA interference-based treatments for chronic and acute diseases.
Parkinson's disease (PD), or simply Parkinson's, is a long-term neurodegenerative disease of mainly the central nervous system that affects both the motor and non-motor systems of the body. The symptoms usually emerge slowly, and as the disease progresses, non-motor symptoms become more common. Usual symptoms include tremors, slowness of movement, rigidity, and difficulty with balance, collectively known as parkinsonism. Parkinson's disease dementia, falls and neuropsychiatric problems such as sleep abnormalities, psychosis, mood swings, or behavioral changes may arise in advanced stages as well.
Bagadilico, Basal Ganglia Disorders Linnaeus Consortium, is a research group in Lund, Sweden, and a Linnaeus environment, supported by the Swedish Research Council. The group comprises about 120 researchers at either Lund University or Lund University Hospital.
Gene therapy in Parkinson's disease consists of the creation of new cells that produce a specific neurotransmitter (dopamine), protect the neural system, or the modification of genes that are related to the disease. Then these cells are transplanted to a patient with the disease. There are different kinds of treatments that focus on reducing the symptoms of the disease but currently there is no cure.
Lorenz Studer is a Swiss biologist. He is the founder and director of the Center for Stem Cell Biology at Memorial-Sloan Kettering Cancer Center in New York City. He is a developmental biologist and neuroscientist who is pioneering the generation of midbrain dopamine neurons for transplantation and clinical applications. His expertise in cell engineering spans a wide range of cells/tissues within the nervous system geared toward disease modeling and exploring cell replacement therapy. Currently, he is a member of the Developmental Biology Program and Department of Neurosurgery at Memorial Sloan-Kettering Cancer Center and a Professor of Neuroscience at Weill Cornell Medical College in New York City, NY.
Blarcamesine is an experimental drug developed by Anavex Life Sciences.
Unity Biotechnology, Inc. is a publicly traded American biotechnology company that develops drugs that target senescent cells.
The Shake It Up Australia Foundation (SIUAF) is an Australian non-for-profit foundation founded in 2011 by Clyde and Greg Campbell. It is partnered with the Michael J. Fox Foundation (MJFF) to achieve the foundations primary aims of "promoting and funding Parkinson's disease research in Australia to slow, stop and cure the disease". Together MJFF and SIUAF are the largest non-government funders of Parkinson's research across multiple institutes in Australia. Since its founding, the foundation has co-founded 38 Parkinson's research projects across 12 institutes to the value of over $10.8 million. The foundation's funding model ensures that 100% of proceeds goes towards Parkinson's research in Australia. This is possible due to the founding directors covering all overhead costs and expenses. In January 2019, Shake It Up are one of the partner organisation in the Australian Parkinson's Mission which was awarded a $30 million-dollar grant to test repurposed drugs in clinical trials.
Ulotaront is an investigational antipsychotic that is undergoing clinical trials for the treatment of schizophrenia and Parkinson's disease psychosis. The medication was discovered in collaboration between PsychoGenics Inc. and Sunovion Pharmaceuticals using PsychoGenics' behavior and AI-based phenotypic drug discovery platform, SmartCube. Ulotaront is in Phase III of clinical development.
Relief Therapeutics is a Swiss biopharmaceutical company based in Geneva. The company focuses on developing drugs for serious diseases with few or no existing treatment options. Its lead compound, RLF-100, is a synthetic form of a natural peptide that protects the lung. The company was incorporated as Relief Therapeutics Holdings AG (RFLB.S) and listed on the SIX Swiss Exchange in 2016.
Peter Elliott is a British pharmacologist and drug developer who has initiated clinical trials across a range of disease areas, and is the co-developer of Velcade, a drug used to treat multiple myeloma.
References
- 1 2 Paddock, Catharine (December 17, 2015). "New drug that protects dopamine cells raises treatment hope for Parkinson's". Medical News Today. Retrieved December 18, 2015.
- 1 2 "Pioneering Neuroprotective Results Achieved in Parkinson's Disease Preclinical Studies". PR Newswire. December 16, 2015. Retrieved December 21, 2015.
- ↑ Azevedo, Margarida (December 21, 2015). "New Drug Candidate Shows Promise in Animal Model of Parkinson's". Parkinson's News Today. Retrieved December 21, 2015.
- 1 2 3 Block, Jonathan (December 17, 2015). "Drug That Protects Dopamine Cells Eyed as Parkinson's Treatment". Phychiatry Advisor. Retrieved December 21, 2015.
- ↑ "Research programme: peptide-based therapeutics - Longevity Biotech". AdisInsight. January 8, 2018.
Highest Development Phases: Preclinical : Neurological disorders; Type 2 diabetes mellitus