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HistoryAmphetamine was synthesized in 1887 by Lazar Edeleanu at the University of Berlin. It was one of a series of compounds related to the plant derivative Ephedrine, which had been purified two years previously by Nagayoshi Nagai. No medical use was found for amphetamine until the 1900s, when it was introduced in most of the world in the form of the pharmaceutical Benzedrine. This drug was used by the militaries of several nations, especially the air forces, to fight fatigue and increase alertness among servicemen. After decades of reports of abuse, the FDA banned Benzedrine inhalers, and limited amphetamines to prescription use in 1959, but illegal use became common. The related compound methamphetamine was first synthesized from ephedrine in Japan in 1893 by chemist Nagayoshi Nagai. In 1919, crystallized methamphetamine was synthesized by Akira Ogaberlandierita via reduction of ephedrine using red phosphorus and iodine. The German military was notorious for their use of methamphetamine in World War Two. In 1997[1] and 1998,[2] researchers at Texas A&M University reported finding amphetamine and methamphetamine in the foliage of two Acacia species native to Texas, A. berlandieri and A. rigidula. Previously, both of these compounds had been thought to be human inventions.[3] Chemistry
Traditionally the medical drug came in the racemic salt d, l-amphetamine sulfate (racemic amphetamine contains levo- and dextro-form in equal amounts). Today, dextroamphetamine sulphate is the predominant form of the drug used; it consists entirely of the d-isomer. Attention disorders are often treated using Adderall or a generic equivalent, a formulation of mixed amphetamine salts that contain both d/l-amphetamine and d-amphetamine in the sulfate and saccharate forms mixed to a final ratio of 3 parts d-amphetamine to 1 part l-amphetamine. PharmacologyAmphetamine, both as d-amphetamine (dextroamphetamine) and l-amphetamine (or a racemic mixture of the two isomers), is believed to exert its effects by binding to the monoamine transporters and increasing extracellular levels of the biogenic amines dopamine, norepinephrine and serotonin. It is hypothesized that d-amphetamine acts primarily on the dopaminergic systems, while l-amphetamine is comparatively norepinephrinergic. The primary reinforcing and behavioral-stimulant effects of amphetamine, however, are linked to enhanced dopaminergic activity, primarily in the mesolimbic DA system. Amphetamine binds to the dopamine transporter (DAT) and blocks the transporters ability to clear DA from the synaptic space. In addition, amphetamine is transported into the cell which leads to dopamine efflux (DA is transported out of the cell and into the synaptic space via reverse transport of the DAT). Medicinal use
Along with methylphenidate (Ritalin, Concerta, etc.), amphetamine is one of the standard treatments for ADHD. Beneficial effects for ADHD can include improved impulse control, improved concentration, decreased sensory overstimulation, and decreased irritability. These effects can be dramatic, particularly in young children. The ADHD medication Adderall is composed of four different amphetamine salts, and Adderall XR is a timed release formulation of these same salt forms. When used within the recommended doses, side-effects like loss of appetite tend to decrease over time. However, amphetamines last longer in the body than methylphenidate (Ritalin, Concerta, etc.), and tend to have stronger side-effects on appetite and sleep.[citation needed] Amphetamines are also a standard treatment for narcolepsy as well as other sleeping disorders. They are generally effective over long periods of time without producing addiction or physical dependence. Amphetamines are sometimes used to augment anti-depressant therapy in treatment-resistant depression. Medical use for weight loss is still approved in some countries, but is regarded as obsolete and dangerous in others. Effects of useAmphetamines release stores of norepinephrine and dopamine from nerve endings by converting the respective molecular transporters into open channels. Amphetamine also releases stores of serotonin from synaptic vesicles when taken in relatively high doses. This effect is more pronounced in methamphetamine use. Like methylphenidate (Ritalin), amphetamines also prevent the monoamine transporters for dopamine and norepinephrine from recycling them (called reuptake inhibition), which leads to increased amounts of dopamine and norepinephrine in synaptic clefts. These combined effects rapidly increase the concentrations of the respective neurotransmitters in the synaptic cleft, which promotes nerve impulse transmission in neurons that have those receptors. Physical effects
Psychological effects
AddictionTolerance is developed rapidly in amphetamine abuse, therefore increasing the amount of the drug that is needed to satisfy the addiction.[4] Many abusers will repeat the amphetamine cycle by taking more of the drug during the withdrawal. This leads to a very dangerous cycle and may involve the use of other drugs to get over the withdrawal process. Chronic abusers of amphetamines typically snort or resort to drug injection to experience the full effects of the drug in a faster and more intense way, with the added risks of infection, vein damage and higher risk of overdose. Harm reduction approach to amphetamine useProponents of the harm reduction philosophy seek to minimize the harms that arise from the recreational use of amphetamines. Safer means of taking the drug—smoked, nasal, oral, and rectal—are encouraged due to the lower risk of overdose, infection, and contraction of bloodborne viruses associated with drug injection. Smoking drugs reveals their effects almost as fast as by injection, as blood directly picks up the drug at the lungs. Amphetamine, contrary to methamphetamine, isn´t smokable. Where the strength of the drug is unknown, users are encouraged to try a small amount first to gauge the strength, to minimize the risks of overdose. For the same reason, poly drug use (the use of two or more drugs at the one time) is discouraged. Users are also encouraged to not use amphetamines alone, as others can assist in the event of an overdose or amphetamine psychosis. Amphetamine users who choose to inject should always use new needles and syringes where possible, and not share these with other users. Governments that support a harm reduction approach often supply new needles and syringes on a confidential basis, as well as education on proper filtering prior to injection, safer injection techniques, and safe disposal of used injecting gear. Legal issues
Internationally, amphetamine is a Schedule II drug under the Convention on Psychotropic Substances.[6] Image:Methamphetamines.png A chart comparing the chemical structures of different amphetamine derivatives Books
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