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Serotonergic 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. Some ...
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6-Hydroxydopamine
Oxidopamine, also known as 6-hydroxydopamine (6-OHDA) or 2,4,5-trihydroxyphenethylamine, is a neurotoxic synthetic organic compound used by researchers to selectively destroy dopaminergic and noradrenergic neurons in the brain. The main use for oxidopamine in scientific research is to induce Parkinsonism in laboratory animals by lesioning the dopaminergic neurons of the substantia nigra pars compacta, in order to develop and test new medicines and treatments for Parkinson's disease. History The neurontoxin oxidopamine has first been described in 1959. Years later, in 1968 the first model exploiting oxidopamine neurotoxicity was developed by Ungerstedt, obtaining an animal model of akineasia with a very high mortality rate. Ever since, oxidopamine has become an abundantly used neurotoxin for making animal models with Parkinson’s disease. Usage The toxin oxidopamine, an antagonist of the neurotransmitter dopamine, and is commonly used for making experimental animal models ...
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Monoamine Releasing Agent
A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of a monoamine neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs induce their effects in the body and/or brain via the release of monoamine neurotransmitters, e.g., trace amines, many substituted amphetamines, and related compounds. Types of MRAs MRAS can be classified by the monoamines they mainly release, although these drugs lie on a spectrum. * Selective for one neurotransmitter ** Serotonin releasing agent (SRA) ** Norepinephrine releasing agent (NRA) ** Dopamine releasing agent (DRA) * Non-selective, releasing two or more neurotransmitters ** Norepinephrine–dopamine releasing agent (NDRA) ** Serotonin–norepinephrine releasing agent (SNRA) ** Serotonin–dopamine releasing agent (SDRA) ** Serotonin–norepinephrine–dopamine releasing agent (SNDRA) Mechani ...
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2,4,5-Trihydroxymethamphetamine
2,4,5-Trihydroxymethamphetamine (THMA or THM) is a neurotoxin and a metabolite of MDMA. It has structural similarity to the dopamine neurotoxin 6-hydroxydopamine, and produces lasting serotonin deficits when administered centrally. See also * 2,4,5-Trihydroxyamphetamine (THA) * 3,4-Dihydroxyamphetamine (HHA; α-methyldopamine) * 3,4-Dihydroxymethamphetamine (HHMA; α-methylepinine) * 4-Hydroxy-3-methoxyamphetamine (HMA) * 4-Hydroxy-3-methoxymethamphetamine 4-Hydroxy-3-methoxymethamphetamine (HMMA) is an active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body ... (HMMA) References Human pathological metabolites Methamphetamines Monoaminergic neurotoxins Recreational drug metabolites {{Neurotoxin-stub ...
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2,4,5-Trihydroxyamphetamine
2,4,5-Trihydroxyamphetamine (THA) is a neurotoxin and a metabolite of MDMA. It comes from the ring-hydroxylation of 3,4-methylenedioxyamphetamine (MDA). In one paper, it was shown to reduce hippocampal tryptophan hydroxylase activity by 54% after short-term treatment. In another study, it was shown to significantly reduce striatal tyrosine hydroxylase activity. See also * 2,4,5-Trihydroxymethamphetamine (THMA) * 3,4-Dihydroxyamphetamine (HHA; α-methyldopamine) * 3,4-Dihydroxymethamphetamine (HHMA; α-methylepinine) * 4-Hydroxy-3-methoxyamphetamine (HMA) * 4-Hydroxy-3-methoxymethamphetamine 4-Hydroxy-3-methoxymethamphetamine (HMMA) is an active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body ... (HMMA) References Human pathological metabolites Monoaminergic neurotoxins Substituted amphetamines Recreational drug metabolites ...
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2,4-Dichloroamphetamine
2,4-Dichloroamphetamine (2,4-DCA) is a psychostimulant of the amphetamine family and a potent serotonergic neurotoxin related to ''para''-chloroamphetamine (PCA; 4-chloroamphetamine). It is also a potent monoamine oxidase inhibitor. See also * 3-Chloroamphetamine (3-CA) * 3,4-Dichloroamphetamine 3,4-Dichloroamphetamine (DCA), is an amphetamine derived drug invented by Eli Lilly in the 1960s, which has a number of pharmacological actions. It acts as a highly potent and selective serotonin releasing agent (SSRA) and binds to the seroto ... (3,4-DCA) References Chloroarenes Monoamine oxidase inhibitors Monoaminergic neurotoxins Substituted amphetamines Stimulants {{Nervous-system-drug-stub ...
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Psychiatric Disorder
A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitting, or occur as single episodes. Many disorders have been described, with signs and symptoms that vary widely between specific disorders. Such disorders may be diagnosed by a mental health professional, usually a clinical psychologist or psychiatrist. The causes of mental disorders are often unclear. Theories may incorporate findings from a range of fields. Mental disorders are usually defined by a combination of how a person behaves, feels, perceives, or thinks. This may be associated with particular regions or functions of the brain, often in a social context. A mental disorder is one aspect of mental health. Cultural and religious beliefs, as well as social norms, should be taken into account when making a diagnosis. Services are b ...
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Memory Impairment
Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use of various sedatives and hypnotic drugs. The memory can be either wholly or partially lost due to the extent of damage that was caused. There are two main types of amnesia: retrograde amnesia and anterograde amnesia. Retrograde amnesia is the inability to retrieve information that was acquired before a particular date, usually the date of an accident or operation. In some cases the memory loss can extend back decades, while in others the person may lose only a few months of memory. Anterograde amnesia is the inability to transfer new information from the short-term store into the long-term store. People with anterograde amnesia cannot remember things for long periods of time. These two types are not mutually exclusive; both can occur simul ...
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Cognitive Impairment
Cognitive deficit is an inclusive term to describe any characteristic that acts as a barrier to the cognition process. The term may describe * deficits in overall intelligence (as with intellectual disabilities), * specific and restricted deficits in cognitive abilities (such as in learning disorders like dyslexia), * neuropsychological deficits (such as in attention, working memory or executive function), * or it may describe drug-induced impairment in cognition and memory (such as that seen with alcohol, glucocorticoids, and the benzodiazepines.) Cause It usually refers to a durable characteristic, as opposed to altered level of consciousness, which may be acute and reversible. Cognitive deficits may be inborn or caused by environmental factors such as brain injuries, neurological disorders, or mental illness. Screening Screening for cognitive impairment in those over the age of 65 without symptoms is of unclear benefit versus harm as of 2020. In a large population-b ...
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Parkinson's Disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms become more common. The most obvious early symptoms are tremor, rigidity, slowness of movement, and difficulty with walking. Cognitive and behavioral problems may also occur with Depression (mood), depression, anxiety, and apathy occurring in many people with PD. Parkinson's disease dementia becomes common in the advanced stages of the disease. Those with Parkinson's can also have problems with their sleep and sensory systems. The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain, leading to a dopamine deficit. The cause of this cell death is poorly understood, but involves the build-up of protein, misfolded proteins into Lewy bodies in the neurons. Collectively, the main motor sym ...
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Metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, catalytic activity of their own (usually as a cofactor to an enzyme), defense, and interactions with other organisms (e.g. pigments, odorants, and pheromones). A primary metabolite is directly involved in normal "growth", development, and reproduction. Ethylene exemplifies a primary metabolite produced large-scale by industrial microbiology. A secondary metabolite is not directly involved in those processes, but usually has an important ecological function. Examples include antibiotics and pigments such as resins and terpenes etc. Some antibiotics use primary metabolites as precursors, such as actinomycin, which is created from the primary metabolite tryptophan. Some sugars are metabolites, such as fructose or glucose, which ar ...
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Antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricants, to prevent oxidation, and to foods to prevent spoilage, in particular the rancidification of oils and fats. In cells, antioxidants such as glutathione, mycothiol or bacillithiol, and enzyme systems like superoxide dismutase, can prevent damage from oxidative stress. The only dietary antioxidants are vitamins A, C, and E, but the term ''antioxidant'' has also been applied to numerous other dietary compounds that only have antioxidant properties in vitro, with little evidence for antioxidant properties in vivo. Dietary supplements marketed as antioxidants have not been shown to maintain health or prevent disease in humans. History As part of their adaptation from marine life, terrestrial plants began producing non-marine anti ...
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Oxidative Stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O2− ( superoxide radical), OH ( hydroxyl radical) and H2O2 ( hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling. In humans, oxidative stress is thought to be involved in the development of attention deficit hyperactivity disorder, cancer ...
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