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Amphetamine

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Amphetamine is a prescription CNS stimulant commonly used to treat attention-deficit hyperactivity disorder (ADHD) in adults and children. It is also used to treat symptoms of traumatic brain injury and the daytime drowsiness symptoms of narcolepsy and chronic fatigue syndrome. Initially it was more popularly used to diminish the appetite and to control weight. Brand names of the drugs that contain amphetamine include Adderall and Dexedrine. The drug is also used illegally as a recreational club drug and as a performance enhancer. The name amphetamine is derived from its chemical name: alpha-methylphenethylamine. The name is also used to refer to the class of compounds derived from amphetamine, often referred to as the substituted amphetamines.

History

Amphetamine was first synthesized in 1887 by Lazar Edeleanu at the University of Berlin. He named the compound phenylisopropylamine. It was one of a series of compounds related to the plant derivative ephedrine, which had been isolated from Ma-Huang that same year by Nagayoshi Nagai. No pharmacological use was found for amphetamine until 1927, when pioneer psychopharmacologist Gordon Alles resynthesized it. Alles was part of a group of researchers looking for an ephedrine substitute. In 1937, it became available in tablet form. During World War II it was extensively used to combat fatigue and increase alertness in soldiers. After decades of reported abuse, the FDA banned Benzedrine inhalers, and limited amphetamines to prescription use in 1965, but illegal use became common. Amphetamine became a schedule II drug with the passage of the Controlled Substances Act in 1970.

The related compound methamphetamine was first synthesized from ephedrine in Japan in 1918 by chemist Akira Ogata via reduction of ephedrine using red phosphorus and iodine. The German military was notorious for their use of methamphetamine in World War Two. It is also known that Adolf Hitler was receiving daily shots of a medicine that contained certain essential vitamins and amphetamines. The German pharmaceutical Pervitin is an oral pill of which was made available in 1938, but by mid-1941 it became a controlled substance, reportedly because of the amount of time needed for a soldier to rest and recover after use. Military doctors were then given guidelines on how they should issue it.

In 1997 and 1998, 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.

Indications

Indicated for:

Contraindications:
  • CNS Stimulants
  • Agitated states
  • Patients with a history of drug abuse
  • Glaucoma
  • MAOI use

Side effects:

Cardiovascular:

Ear, nose, and throat:

Eye:

Gastrointestinal:

Musculoskeletal:

  • Involuntary movements

Neuropharmacology:

Respiratory:

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, decreased irritability and decreased anxiety. These effects can be dramatic in both young children and adults. 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.

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.

Contradictions

Stimulants such as amphetamines elevate cardiac output and blood pressure making them dangerous for use by patients with a history of heart disease or hypertension. Also, patients with a history of drug dependence or anorexia should not be treated with amphetamines due to their addictive and appetite suppressing properties. Amphetamines can cause a life-threatening complication in patients taking MAOI antidepressants. Amphetamine is not suitable for patients with a history of glaucoma.

Amphetamines have also been shown to pass through into breast milk. Because of this, mothers taking medications containing amphetamines are advised to avoid breastfeeding during their course of treatment.

Pharmacology

Chemical Properties

Amphetamine is a chiral compound. The racemic mixture can be divided into its optical antipodes: levo- and dextro-amphetamine. Amphetamine is the parent compound of its own structural class, comprising a broad range of psychoactive derivatives, e.g., MDMA (Ecstasy) and the N-methylated form, methamphetamine. Amphetamine is a homologue of phenethylamine.

At first, the medical drug came as the salt racemic-amphetamine sulfate (racemic-amphetamine contains both isomers in equal amounts). Today, dextroamphetamine sulfate 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 racemic-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.

Pharmacodynamics

Amphetamine has been shown to both diffuse through the cell membrane and travel via the dopamine transporter (DAT) to increase concentrations of dopamine in the neuronal terminal.

Amphetamine, 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 (noradrenaline) and serotonin. It is hypothesized that d-amphetamine acts primarily on the dopaminergic systems, while l-amphetamine is comparatively norepinephrinergic (noradrenergic). The primary reinforcing and behavioral-stimulant effects of amphetamine, however, are linked to enhanced dopaminergic activity, primarily in the mesolimbic dopamine system. Amphetamine and other amphetamine-type stimulants principally act to release dopamine into the synaptic cleft. The increased amphetamine concentration releases endogenous stores of dopamine from vesicular monoamine transporters (VMATs), thereby increasing intra-neuronal concentrations of transmitter. This increase in concentration effectively reverses transport of dopamine via the dopamine transporter (DAT) into the synapse. In addition, amphetamine binds reversibly to the DATs and blocks the transporter's ability to clear DA from the synaptic space. Amphetamine also acts in this way with norepinephrine (noradrenaline) and to a lesser extent serotonin.

In addition, amphetamine binds to a group of receptors called TrAce Amine Receptors (TAAR). TAAR are a newly discovered receptor system which seems to be affected by a range of amphetamine-like substances called trace amines.

Physical effects

Psychological effects

  • Short-term psychological effects of the drug at therapeutic levels could include alertness, euphoria, increased concentration, rapid talking, increased confidence, and increased social responsiveness . Effects of the drug when abused could include, hallucinations, and loss of REM sleep the night after use .

  • Long-term amphetamine abuse can induce psychological effects that include insomnia, mental states resembling schizophrenia, aggressiveness (not associated with schizophrenia), addiction or dependence with accompanying withdrawal symptoms, irritability, confusion, and panic . Chronic and/or extensively-continuous use can lead to amphetamine psychosis, which causes delusions and paranoia, but this is uncommon when taken as prescribed. The abuse of an amphetamine is highly addictive, and, with chronic abuse, tolerance develops very quickly. Withdrawal, although not physiologically threatening, is an unpleasant experience (including paranoia, depression, difficult breathing, dysphoria, gastric fluctuations and/or pain, and lethargia) . This commonly leads chronic users to re-dose amphetamine frequently, explaining tolerance and increasing the possibility of addiction.

Dependence & Addiction

Tolerance is developed rapidly in amphetamine abuse, therefore increasing the amount of the drug that is needed to satisfy the addiction. Repeated amphetamine use can produce "reverse tolerance", or sensitization to some psychological effects. 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. Abusers will commonly stay up for 2 or 3 days avoiding the withdrawals then dose themselves with benzodiazepines or barbiturates to help them stay calm while they recuperate. The constant switching from uppers to downers can cause serious damage to the CNS and brain . 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. Because of the abuse of amphetamines in the U.S., most brands were discontinued by the 1990s, including the highly abused brand names Biphetamine (known as "black beauties") and Preludin, known on the street as "slams", whose coating was peeled and then injected. Only a few brands of amphetamines are still produced in the United States: those prescribed for narcolepsy, attention-deficit hyperactivity disorder, treatment-resistant depression, and extreme obesity.

Performance-enhancing use

Amphetamine is used by college and high-school students as a study and test-taking aid. Amphetamine increases energy levels, concentration, and motivation, allowing students to study for an extended period of time. These drugs are often acquired through ADHD prescriptions to students and peers, rather than illicitly produced drugs.

Amphetamine is also used by professional, collegiate and high school athletes for its strong stimulant effect. Energy levels are perceived to be dramatically increased and sustained, believed to allow for more vigorous and longer play, though at least one study has found that this effect is not measurable. This practice can be extremely dangerous, and athletes have died as a result, for example, British cyclist Tom Simpson. A doctor (the same doctor who prescribed 800 children Adderall in order to lose weight) has created a diet based around amphetamines, called the adderall diet. CNN ran a story about the diet and the doctor and people expressed outrage.

Amphetamine use has historically been especially common among Major League Baseball (MLB) athletes and is usually known by the slang term "greenies". In 2006, MLB banned the use of amphetamines and the ban is enforced by periodic drug-testing. Consequences if a player tests positive are significant, but MLB has received some criticism because these consequences are dramatically less severe than for steroids, with the first offense bringing only a warning and further testing.

Truck drivers, especially long-haul drivers, take amphetamine to combat symptoms of somnolence and to increase their concentration on driving.

Legal issues

  • In the United Kingdom, amphetamines were regarded as Class B drugs. The maximum penalty for unauthorised possession is five years in prison and an unlimited fine. The maximum penalty for illegal supply is fourteen years in prison and an unlimited fine. Methamphetamine has recently been reclassified to Class A, penalties for possession of which are more severe (7 years in prison and an unlimited fine).
  • In the Netherlands, amphetamine and methamphetamine are List I drugs of the Opium Law, but the dextro isomer of amphetamine is indicated for ADD/ADHD and narcolepsy and available for prescription as 5 and generic tablets, and 5 and gelcapsules.
  • In the United States, amphetamine and methamphetamine are Schedule II drugs, classified as CNS (Central Nervous System) Stimulants. A Schedule II drug is classified as one that has a high potential for abuse, has a currently-accepted medical use and is used under severe restrictions, and has a high possibility of severe psychological and physiological dependence.

Internationally, amphetamine is a Schedule II drug under the Convention on Psychotropic Substances.

Books

  • Seabrook, Jeremy (1996). In the Cities of the South: scenes from a developing world. London; New York: Verso. ISBN 1-85984-986-5.

See also

References and notes

External links



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Last updated on Friday March 14, 2008 at 01:38:59 PDT (GMT -0700)
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