Amphetamine’s chemical name is Alpha Methyl Phen Ethyle Amine. This medication stimulates the central nervous system and decreases appetite. It is similar to hormones Adrenaline (also called Epinephrine) and Noradrenaline (Norepinephrine). Amphetamine sulfate is also known under the pharmacopoeia name “Phenamine”.
History

You can look at Amphentamine as at the synthetic analogue of Ephedrine. It was produced in 1887 as a medication that suppressed appetite, but it was soon reported as drug abuse.
During World War II American soldiers always had 10 tablets of Amphetamine packed along with canned food, cigarettes and chewing gum.

When the war was over, and U.S. troops occupied Japan, police started to find strange pills used by teenagers. That was Amphetamine, the drug taken by U.S. pilots and sailors while on duty as a medication that relieved tiredness, fought sleep and improved attention. Hundreds of thousands of teenagers were abusing Amphetamine by 1954.

There were too many Japanese teenagers addicted to Amphetamine in the 1950’s, and this was a signal of the beginning of an epidemic of teenage drug addiction in the second half of XX century. This epidemic quickly spread across the United States and later it moved to Europe. Amphetamine mania especially progressed in England and Sweden.

About 18% of English teenagers who ran away from home or boarding schools and were caught by police had the Amphetamine derivatives in their urine. About 28% of Sweden teenagers were addicted to Amphetamine in 1966, and about 20% of high school students took this drug in California in the early 70’s. In fact this medication quickly spread across the USA without any “region or class division”.

Amphetamines have been produced under the trade name of Benzedrine (benzene – ephedrine) in the USA since 1928. It was used as an inhalation that eased nasal congestion and a stimulant of the central nervous system. Benzedrine was widely used during World War II. This drug became a controlled medication in 1959. It was later gone from pharmacopoeia.

Amphetamines were produced in the former USSR from the 40’s, but they were applied only in medical practice at first and not available for public usage. In the 80’s and 90’s this drug was popular in the Northwest regions of Russia, in Kazakhstan and the Baltic republics.

Since the mid 60’s, reports have been mentioning that teenagers started to take Amphetamine injections. They often substituted it with Methylphenamin and Methylphenidate (Russians also used to call these drugs “Merida”, “Centedrine” or “Ritalin”).

In the 70’s, the Amphetamine abuse among teenagers in the West began to wane. It was replaced by marijuana, heroin, hallucinogens and inhalants.

Amphetamines are still known as “military drugs”. They are included in the U.S. Army Special Forces medical kits. Russians use these medications in the expanded tank and aircraft medical kits. Universal antidote Afin is a combination of holinoblokator and amphetamine.

Synthesis

Because Leuckart reaction is one of the simplest chemical reactions, it is still one of the most popular synthesis schemes used in illegal Amphetamine manufacture.

Leuckart Synthesis allows sample recovery without the usage of metals. This reaction usually has three phases. For the synthesis of Amphetamine, you can at first heat P2P and Formamide (sometimes together with formic acid) or Ammonium formate until you get an intermediate product known as N-formylamphetamine. Then you need to hydrolyze N-formylaphetamine with hydrochloric acid. The reaction mix should be basified, separated and steamed. During the final phase, you obtain precipitate of the product from the reaction solution, usually in the form of suphate. Amphetamine base should look like an oily liquid that has a specific “fish-amine” odor.

Physical and Chemical Properties

Based on structure, Amphetamine belongs to a group of Phenylalkylamine derivatives.

Amphetamine base is a colorless, mobile, heavy liquid that boils at 205 degrees and smells of rotten fish. This odor is typical to the most amines. Base condensed with steam contains a significant amount of water that segregates when heated above 30-40 degrees and dissolves when temperature is falling down. It hardly resolves in the water. It absorbs CO2 from the air and transforms into water-insoluble salt – carbonate.

It is most commonly used as sulfate, phosphate, hydrochloride, oxalate hemihydrate and ascorbate. All these salts look like white crystalline powder that is soluble in water (to varying degrees) and alcohols, and not soluble in ether and chloroform.

Amphetamine hydrochloride is strongly hydroscopic.

Amphetamine has physical properties of stereoisomer. Its two isomers – L and D – have different pharmacological activity levels. D-isomer (Dextroamphetamine) is more active as a stimulant than L-isomer (Levamphetamine).

Pharmacological Action

Sites of Action

D-amphetamine is similar to its analogue methamphetamine. It also acts as an indirect dopamine agonist. It promotes dopamine release from the vesicular pool and inhibits MAO. Besides, Amphetamine affects the activity of dopamine transporter by blocking the “reuptake reaction”. Looking at the striatum cuts of wild mice and in vivo (microdialysis studies); you can notice that Amphetamine causes a gradual increase of extra cellular dopamine while depleting the vesicular pool of dopamine at the same time. This effect wasn’t observed in mice that lacked dopamine transporter gene.

Psychiatric Manifestations

Amphetamine has many stimulatory effects. It increases activity and vitality, reduces tiredness, raises your mood, improves concentration, suppresses appetite and reduces the need for sleep. However, in case of overdose, all these effects become excessive. For example, communication turns into gabbing, and pathological circumstantial speech, etc. Increased activity might be productive, but in case of overdose, it becomes pointless.

Systematic misuse of Amphetamine can lead to schizophrenia-like psychosis. Some patients report severe headaches as a side effect of overdose.

All these effects are caused due to the increase of norepinephrine and dopamine release in the CNS.

Upon the completion of the drug action, these behavioral reactions are followed by a reduced emotional activity that sometimes turns into depressions and exhaustion (this is individually for each person).

The desired effect of amphetamine influence on the body actually meets the entire spectrum of sympathetic nervous system effects: the stress response and mobilization, the predominance of catabolism over anabolism, and others. “Street” amphetamine may contain various admixtures that modify the clinical picture. They can also include slightly toxic organic products, unremoved in the synthesis, and conditionally inert fillers of the original dosage form. Besides this, low-grade under-the-counter drugs can contain dangerous inorganic compounds such as solid or absorbed bases or acids (due to errors in titration), solvents without steam-destination, hazardous osmotically salts, oxidizers that can damage proteins, mercury compounds, nickel, platinum group metals, as well as small insoluble fractions (for example, dust corundum) that can cause mechanical damages.

Such under-the-counter medications can also lead to the following side effects:

– rapid pulse;
– increased blood pressure (mainly due to noradrenaline stimulation of α-adrenergic vascular smooth muscle and β-adrenergic receptors in the heart);

– changes in smooth muscle tone (for example, mydriasis or an excessive dilation of the pupil; vasoconstriction or the narrowing of the blood vessels);

– dry mucous membranes, as well as mucosal damage through direct contact with the drug);
– cold sweat;

– tongue biting and biting the inside of the cheeks;

– teeth clenching (bruxism);

– stereotypes (obsessive repetitive monotonous movements); its opposite effect (expressed “lack of exercise”) is observed rarely, it is usually accompanied by excessive fixation of attention on these and other mental objects that can be long-lasting and, combined with an uncomfortable pose and vasoconstriction problems, it can cause bad blood circulation and even lead to necrosis;

– activization (due to lower esophageal sphincter tone) of duodenogastric and gastroesophageal reflux and other disorders such as constipation, bloating, stomach pain, nausea and vomiting;

– cutting pain while urinating.

Overdose can lead to abnormal work of the cardiovascular system (such as electrolyte imbalance and excess load), and in the future it can cause mental disabilities, all kinds of manifestations of wasting syndrome (including the pathology of kidney, liver diseases).

Cardiovascular disorders include:

– Hypertensive crisis;
– Transient ischemic attack;
– Tachycardia;
– Paroxysm;
– Acute coronary heart diseases such as heart attack and stroke, as well as the development of acute heart failure, and collapse.
In addition, prolonged abuse of this drug often leads to multiple dental caries (due to calcium loss, mechanical impact, changes in environmental conditions in the oral cavity due to decreased salivation, poor tooth brushing and neglecting regular health check-ups).

Application

In Medicine

Amphetamine is a synthetic compound that belongs to the class of phenylalkylamines. Its chemical structure and some pharmacological properties (mainly, by the way it effects peripheral parts of the sympathetic nervous system) make it similar to the drugs of the adrenaline class.

According to its structure, amphetamine is different from adrenaline and noradrenaline because it lacks hydroxyl groups in the aromatic ring and aliphatic chain, which makes it highly resistant and, moreover, makes it easy to overcome the blood-brain barrier. The branched aliphatic chain (the presence of a methyl group in a-position to amino group) protects its molecule from oxidative deamination of monoamine oxidase.

Thanks to its persistence, the amphetamine effects are durable inside the body and kept after being taken inside.

Amphetamine is a strong stimulator of the CNS. Stimulatory effect of this drug is related to its impact on the brain stem.

In the neurochemical mechanism of amphetamine’s action, an important role is given to its ability to release the granules of presynaptic nerve endings of noradrenaline and dopamine, and stimulate the central noradrenergic and dopaminergic receptors this way. It also has a small inhibitory effect on monoamine oxidase activity and inhibits reverse neuronal capture of dopamine and norepinephrine.

Amphetamine is also peripheral adrenergic active. It stimulates the a- and b-adrenergic receptors. It causes peripheral vasoconstriction, increases heartbeat, increases blood pressure, relaxes bronchial muscles, and causes dilated pupils. These effects are more persistent, but less expressed than those caused by adrenaline.

With proper dosing, amphetamine increases the excitation processes in the CNS, reduces the feelings of being tired, has a general stimulating effect that improves mood, gives you the feeling of new strength and energy, increases your efficiency, and reduces the need for sleep. In small doses, it has a positive influence on the formulation and implementation of conditional reflexes, and promotes sexual activity.

Amphetamine and its analogues weaken and shorten your sleep, caused by sleeping pills and narcotics that is why it is sometimes called “awakening amines”.

This is active anorexigenic drug. It suppresses appetite and gives you the feeling of being full.

Amphetamine was considered to be one of the main psychoactive preparations for a long time. Combined with other drugs, it was widely used to improve mental and physical activity, to treat narcolepsy, depression, the effects of encephalitis and other diseases associated with drowsiness, lethargy, apathy, asthenia, and Parkinsonism.

In the recent years, due to its side effects (changes in higher nervous activity, increased blood pressure, frequent paradoxical reactions – drowsiness and apathy rather than excitement, efficiency decrease, etc.) and, most importantly, with the risks of the addiction and habituation development, amphetamine is being used in rare cases.

This drug is prescribed to take orally. Adult dose is 0,005-0,01 g (5-10 mg) taken 1-2 times a day.

The effect after a single dose lasts from 2 to 8 hours.

Dosage must be individualized because the effect varies on sensitivity and tolerance.

The drug stays inside the body for a long time. It can cause cumulation phenomenon.

Amphetamines should be taken with caution and for medical reasons only.

Drug overdose can cause dizziness, chills, nausea, loss of appetite, insomnia, tachycardia, and arrhythmias. Long-term uncontrolled use of it can lead to severe neuropsychiatry disorders, and even schizophrenic psychoses.

If you take amphetamine in the afternoon, it can disrupt your sleep.

This drug is released strictly on the prescription of a licensed doctor (in countries where it’s legal to use).

Contraindications to the use of amphetamine:

– old age;
– insomnia;
– overexcitement;
– liver disease;
– hypertension;
– atherosclerosis;
– organic diseases of the cardiovascular system.
Recreational Use

The usage of amphetamine and some of its precursors is limited in Russia. Despite this fact, it is often used as a stimulant to improve concentration and efficiency by students, as well as a popular club drug. It is used alone or in addition to “Ecstasy”. This is because amphetamine itself has a physical rather than psychological impact on most consumers.

When taken regularly, amphetamine quickly leads to psychological dependency. Its first manifestation is an irresistible desire to repeat the dose of amphetamine or to take it again in post-intoxication period. By this, patients are trying to avoid depressed mood, and somatic discomfort. Regular use of amphetamine stimulant causes drug effects disappear. To get pleasant sensations again, a drug addict is forced to increase his dose. Tolerance increases during the first few weeks of systematic intake of this medicine.

There are different methods of taking amphetamine:

– orally (in pills form or powder);
– insufflation of the powder up the nose;
– inhalation (through smoking a mixture of amphetamine salts and alkali);
– parenterally (intravenous, sometimes through intramuscular injections; subcutaneous injection is not common);
– rectally (melted suppository enema or solution as an enema).

Usually amphetamine is illegally distributed in the form of stimulating mixtures containing amphetamine salt (mostly phenamine-racemate) and its tarring products (they often give the drug a pink color), technological admixtures (benzyl methyl ketone, mirabilite, magnesium sulfate, N-formyl amphetamine, benzene, etc. depending on the method of its manufacture), biologically active substances (such as caffeine, piracetam, cyclodolum) and fillers used to increase the mixture’s weight.

Amphetamine and its analogues are included in a number of preparations that are used to control body weight, and are not certified in Russia. They are also contained in many under-the-counter preparations for “weight loss” that are sold under the looks of other medicines, dietary supplements, etc.

According to the slang of drug addicts, amphetamine is often called “speed”, “amph”; “phen” (this is a short form of the trade name “Phenamine”); rarely “alarm” and other names. Collective names for this drug group of amphetamines in particular and stimulators in general are “vitamin”, “powder” and “white.”
Clinics, diagnostics

Diagnosis of amphetamine intoxication is based on the analysis of mental symptoms and somatic-vegetative symptoms that signal about a tension of adrenergic system. This includes such symptoms as paleness of distal extremities, increased blood pressure, tachycardia, dry skin, dilated pupils, and hyperglycemia.

The greatest danger is the possibility of developing a psychotic excitement that is accompanied by antisocial behavior.