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2′-CH3-MPTP
2′-CH3-MPTP, also known as 2′-methyl-MPTP, is a selective dopaminergic neurotoxin related to MPTP which is used in scientific research to lesion dopaminergic neurons. It is a considerably more potent dopaminergic neurotoxin than MPTP in mice but is less potent than MPTP in primates. MPTP and 2′-CH3-MPTP produce a Parkinson's disease-like condition in animals. 2′-CH3-MPTP is metabolized by monoamine oxidase A (MAO-A) and B (MAO-B) and this biotransformation is required for its dopaminergic neurotoxicity. Whereas the dopaminergic neurotoxicity of MPTP is completely prevented by the MAO-B inhibitor selegiline, complete prevention of 2′-CH3-MPTP's dopaminergic neurotoxicity requires combined treatment with both selegiline and the MAO-A inhibitor clorgyline. A close analogue of 2′-CH3-MPTP is 2′-NH2-MPTP, which, in contrast to 2′-CH3-MPTP and MPTP, is a serotonergic and noradrenergic neurotoxin with no effect on dopaminergic neurons. Numerous other neurotoxi ...
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Dopaminergic 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 ...
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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 ...
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Monoaminergic Neurotoxins
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 ...
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2′-NH2-MPTP
2′-NH2-MPTP, also known as 2′-amino-MPTP, is a monoaminergic neurotoxin that was derived from MPTP and is used in scientific research to lesion brain monoaminergic systems in animals. Whereas MPTP is a selective dopaminergic neurotoxin, 2′-NH2-MPTP is a specific serotonergic and noradrenergic neurotoxin that does not affect dopaminergic neurons. 2′-NH2-MPTP is transported by the serotonin transporter (SERT) into serotonergic neurons and by the norepinephrine transporter (NET) into noradrenergic neurons, and its serotonergic and noradrenergic neurotoxicity is dependent on this transport by the SERT and NET, respectively. 2′-NH2-MPTP was first described in the scientific literature Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical ... by 1993. See also * 2′-CH3-MPTP ...
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Dopaminergic 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 ...
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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 ...
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Scientific Literature
Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical contributions. These papers serve as essential sources of knowledge and are commonly referred to simply as "the literature" within specific research fields. The process of academic publishing involves disseminating research findings to a wider audience. Researchers submit their work to reputable journals or conferences, where it undergoes rigorous evaluation by experts in the field. This evaluation, known as peer review, ensures the quality, validity, and reliability of the research before it becomes part of the scientific literature. Peer-reviewed publications contribute significantly to advancing our understanding of the world and shaping future research endeavors. Original scientific research first published in scientific journals co ...
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Chemical Synthesis
Chemical synthesis (chemical combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In modern laboratory uses, the process is reproducible and reliable. A chemical synthesis involves one or more compounds (known as '' reagents'' or ''reactants'') that will experience a transformation under certain conditions. Various reaction types can be applied to formulate a desired product. This requires mixing the compounds in a reaction vessel, such as a chemical reactor or a simple round-bottom flask. Many reactions require some form of processing (" work-up") or purification procedure to isolate the final product. The amount produced by chemical synthesis is known as the '' reaction yield''. Typically, yields are expressed as a mass in grams (in a laboratory setting) or as a percentage of the total theoretical quantity that could be produced based ...
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Structural Analog
A structural analog, also known as a chemical analog or simply an analog, is a chemical compound, compound having a chemical structure, structure similar to that of another compound, but differing from it in respect to a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced with other atoms, groups, or substructures. A structural analog can be imagined to be formed, at least theoretically, from the other compound. Structural analogs are often isoelectronicity, isoelectronic. Despite a high chemical similarity, structural analogs are not necessarily functional analog (chemistry), functional analogs and can have very different physical, chemical, biochemical, or pharmacological properties. In drug discovery, either a large series of structural analogs of an initial lead compound are created and tested as part of a structure–activity relationship study or a database is virtual screening, screened for structural analogs of a ...
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Clorgyline
Clorgiline (INN), or clorgyline ( BAN), is a monoamine oxidase inhibitor (MAOI) structurally related to pargyline which is described as an antidepressant. Specifically, it is an irreversible and selective inhibitor of monoamine oxidase A (MAO-A). Clorgiline was never marketed, but it has found use in scientific research. It has been found to bind with high affinity to the σ1 receptor (Ki = 3.2 nM) and with very high affinity to the I2 imidazoline receptor (Ki = 40 pM). Unlike selegiline, clorgiline does not appear to be a monoaminergic activity enhancer Monoaminergic activity enhancers (MAE), also known as catecholaminergic/serotonergic activity enhancers (CAE/SAE), are a class of drugs that enhance the action potential-evoked release of monoamine neurotransmitters in the nervous system. MAEs ar ... (MAE). Clorgiline is also a multidrug efflux pump inhibitor. Holmes ''et al.'', 2012 reverse azole fungicide resistance using clorgiline, showing promise for its u ...
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