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MPTP
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is an organic compound. It is classified as a tetrahydropyridine. It is of interest as a precursor to the monoaminergic neurotoxin MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain. It has been used to study disease models in various animals. While MPTP itself has no psychoactive effects, the compound may be accidentally produced during the manufacture of MPPP, a synthetic opioid drug with effects similar to those of morphine and pethidine (meperidine). The Parkinson-inducing effects of MPTP were first discovered following accidental injection as a result of contaminated MPPP. Toxicity Injection of MPTP causes rapid onset of Parkinsonism, hence users of MPPP contaminated with MPTP will develop these symptoms. MPTP itself is not toxic, but it is a lipophilic compound and can therefore cross the blood–brain barrier. Once inside the brai ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Monoaminergic Neurotoxin
A monoamine neurotoxin, or monoaminergic neurotoxin, is a drug that selectively damages or destroys monoaminergic neurons. Monoaminergic neurons are neurons that signal via stimulation by monoamine neurotransmitters including serotonin, dopamine, and norepinephrine. Examples of monoamine neurotoxins include the serotonergic neurotoxins ''para''-chloroamphetamine (PCA), methylenedioxymethamphetamine (MDMA), and 5,7-dihydroxytryptamine (5,7-DHT); the dopaminergic neurotoxins oxidopamine (6-hydroxydopamine), MPTP, and methamphetamine; and the noradrenergic neurotoxins oxidopamine and DSP-4. In the case of serotonergic neurotoxins like MDMA, research suggests that simultaneous induction of serotonin and dopamine release, serotonin depletion, dopamine uptake and metabolism, hyperthermia, oxidative stress and antioxidant depletion, and/or drug metabolites may all be involved in the neurotoxicity. On the other hand, there is evidence that drug metabolites may not be involved. So ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
1-methyl-4-phenylpyridinium
MPP+ (1-methyl-4-phenylpyridinium) is a positively charged organic molecule with the chemical formula C12H12N+. It is a monoaminergic neurotoxin that acts by interfering with oxidative phosphorylation in mitochondria by inhibiting complex I, leading to the depletion of ATP and eventual cell death. MPP+ arises in the body as the toxic metabolite of the closely related compound MPTP. MPTP is converted in the brain into MPP+ by the enzyme MAO-B, ultimately causing parkinsonism in primates by killing certain dopamine-producing neurons in the substantia nigra. The ability for MPP+ to induce Parkinson's disease has made it an important compound in Parkinson's research since this property was discovered in 1983. The chloride salt of MPP+ found use in the 1970s as an herbicide under the trade name cyperquat. Though no longer in use as an herbicide, cyperquat's closely related structural analog paraquat still finds widespread usage, raising some safety concerns. History MPP+ has bee ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Substantia Nigra
The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the substantia nigra appears as a continuous band in brain sections, anatomical studies have found that it actually consists of two parts with very different connections and functions: the pars compacta (SNpc) and the pars reticulata (SNpr). The pars compacta serves mainly as a projection to the basal ganglia circuit, supplying the striatum with dopamine. The pars reticulata conveys signals from the basal ganglia to numerous other brain structures. Structure The substantia nigra, along with four other nuclei, is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MPPP
Desmethylprodine or 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP, Ro 2-0718) is an opioid analgesic drug developed in the 1940s by researchers at Hoffmann-La Roche. Desmethylprodine has been labeled by the DEA as a Schedule I drug in the United States. It is an analog of pethidine (meperidine) a Schedule II drug. Chemically, it is a reversed ester of pethidine which has about 70% of the potency of morphine. Unlike its derivative prodine, it does not exhibit optical isomerism. It was reported to have 30 times the activity of pethidine and a greater analgesic effect than morphine in rats, and it was demonstrated to cause central nervous system stimulation in mice. History Desmethylprodine was first synthesized in 1947 at Hoffman-LaRoche Laboratories by Albert Ziering and John Lee. They found that it produced effects similar to morphine when administered to rats. Ziering had been searching for synthetic painkillers that were less addictive than morphine. The new drug was a s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Parkinson's Disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become more prevalent as the disease progresses. The motor symptoms are collectively called parkinsonism and include tremors, bradykinesia, spasticity, rigidity as well as postural instability (i.e., difficulty maintaining balance). Non-motor symptoms develop later in the disease and include behavior change (individual), behavioral changes or mental disorder, neuropsychiatric problems such as sleep abnormalities, psychosis, anosmia, and mood swings. Most Parkinson's disease cases are idiopathic disease, idiopathic, though contributing factors have been identified. Pathophysiology involves progressive nerve cell death, degeneration of nerve cells in the substantia nigra, a midbrain region that provides dopamine to the basal ganglia, a system invo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Parkinsonism
Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), Rigidity (neurology), rigidity, and balance disorder, postural instability. Both hypokinetic features (bradykinesia and akinesia) and hyperkinetic features (cogwheel rigidity and tremors at rest) are displayed in parkinsonism. These are the four Parkinson's disease#Motor, motor signs that are found in Parkinson's disease (PD)after which Parkinsonism is namedand in dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and many other conditions. This set of signs occurs in a wide range of conditions and may have many causes, including neurodegenerative conditions, drugs, toxins, metabolic diseases, and neurological conditions other than Parkinson's disease. Signs and symptoms Parkinsonism is a clinical syndrome characterized by the four Parkinson's disease#Motor, motor signs that are found in Parkinson's disease: tremor, bradykinesia (slowed movements), Rigidity (neur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Selegiline
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 and used off-label 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. Side effects of selegiline occurring more often than with placebo include insomnia, dry mouth, dizziness, anxiety, abnormal dreams, and application site reactions (with the patch form), among others. At high doses, selegiline has the potential for dangerous food and drug interactions, such as tyramine-related hypertens ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tetrahydropyridine
Tetrahydropyridines (or piperideines) are heterocycles with the formula . Three isomers exist, which differ by the location of the double bond. None of the parent species occur widely, so they are mainly of theoretical interest. Although the parent tetrahydropyridines are rare, many substituted tetrahydropyridines are known. Preparation and occurrence 2,3,4,5-Tetrahydropyridine, a colorless liquid, is commercially available. It is an imine. Illustrating another isomer of tetrahydropyridine, 6-acetyl-2,3,4,5-tetrahydropyridine occurs naturally. Partial reduction of pyridinium salts gives N-alkyltetrahydropyridines. Treatment of N-methylpyridinium with borohydride Borohydride refers to the anion , which is also called tetrahydroborate or more commonly tetrahydrobiopterin, and its salts. Borohydride or hydroborate is also the term used for compounds containing , where ''n'' is an integer from 0 to 3, for ex ... reagents gives 1-methyl-1,2,3,6-tetrahydropyridine. A modified ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pars Compacta
The pars compacta (SNpc, SNc) is one of two subdivisions of the ''substantia nigra'' of the midbrain (the other being the pars reticulata); it is situated medial to the ''pars reticulata''. It is formed by dopaminergic neurons. It projects to the striatum and portions of the cerebral cortex. It is functionally involved in fine motor control. Parkinson's disease is characterized by the death of dopaminergic neurons in this region. Anatomy In humans, the nerve cell bodies of the ''pars compacta'' are coloured black by the pigment neuromelanin. The degree of pigmentation increases with age. This pigmentation is visible as a distinctive black stripe in brain sections and is the origin of the name given to this volume of the brain. Microanatomy The neurons have particularly long and thick dendrites. The ventral dendrites, particularly, go down deeply in the pars reticulata. Other similar neurons are more sparsely distributed in the midbrain and constitute "groups" with no well-def ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dopaminergic
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic pathways, Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that Biosynthesis, synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as ''dopaminergic''. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol-O-methyl transferase, catechol ''O''-methyl transferase (COMT) may be referred to as ''dopaminergic'' as well. Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release thro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dopamine Transporter
The dopamine transporter (DAT, also sodium-dependent dopamine transporter) is a membrane-spanning protein coded for in humans by the ''SLC6A3'' gene (also known as ''DAT1''), that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dopamine into Vesicle (biology and chemistry), vesicles for storage and later release. Dopamine reuptake via DAT provides the primary mechanism through which dopamine is cleared from synapses, although there may be an exception in the prefrontal cortex, where evidence points to a possibly larger role of the norepinephrine transporter. DAT is implicated in a number of dopamine-related disorders, including ADHD, attention deficit hyperactivity disorder, bipolar disorder, clinical depression, eating disorders, and substance use disorders. The gene that encodes the DAT protein is located on chromosome 5, consists of 15 coding exons, and is roughly 64 base pair#Length measuremen ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
