D/L-AMPHETAMINE HYDROCHLORIDE

Absorption

Amphetamine is well absorbed in the gut and as it is a weak base hence the more basic the environment the more of the drug is found in a lipid-soluble form and the absorption through lipid-rich cell membranes is highly favored. The peak response of amphetamine occurs 1-3 hours after oral administration and approximately 15 minutes after injection and it presents a bioavailability of over 75%. Complete amphetamine absorption is usually done after 4-6 hours.

Toxicity

The mean lethal serum concentration is reported to be of 6.4 mg/l. Acute amphetamine overdose can lead to hyperthermia, respiratory depression, seizures, metabolic acidosis, renal failure, hepatic injury, and coma. Some of the neurologic effects have been shown to be agitation, aggressive behavior, irritability, headache, and hallucinations. In the cardiovascular site, there have been reports of arrhythmia, cardiomyopathy, myocardial infarction or ischemic stroke. Lastly, in the GI tract, there are reports if abdominal pain, vomiting, diarrhea, cramps, anorexia and GI hemorrhage. A dose of 1-2 g of amphetamine is known to cause severe intoxication but some chronic abusers can report usage of even 5-15 g per day.
In animal studies, there is no evidence of carcinogenic potential, not clastogenic or to affect fertility or early embryonic development.

Description

Amphetamine is a mobile liquid with an amineodor. Molecular weight= 135.23; Boiling point=200°203℃; Flash point #100℃. Hazard Identification(based on NFPA-704 M Rating System): Health 4,Flammability 1, Reactivity 0. Slightly soluble in water.

Chemical properties

Colorless, volatile liquid; characteristic strong odor; slight burning taste. Soluble in alcohol and ether; slightly soluble in water.

Chemical properties

Amphetamine is a mobile liquid with an amine odor.

The Uses of D/L-AMPHETAMINE HYDROCHLORIDE

Stimulant (central).

The Uses of D/L-AMPHETAMINE HYDROCHLORIDE

Amphetamine is the basis of a group of hallucinogenic, habit-forming drugs that affect the central nervous system. The drug also finds medical application, notably in appetite suppressants. It should be emphasized that administration of amphetamines for prolonged periods in connection with weight-reduction programs may lead to drug dependence. Professionals must pay particular attention to the possibility of persons obtaining amphetamines for nontherapeutic use or distribution to others.

The Uses of D/L-AMPHETAMINE HYDROCHLORIDE

Amphetamines are advocated for use in a wide variety of conditions but are medically approved for the treatment of attention-deficit hyperactivity disorder, narcolepsy, and weight loss. Amphetamines are also popular drugs of abuse available in several forms for different routes of abuse.

Background

Amphetamine, a compound discovered over 100 years ago, is one of the more restricted controlled drugs. It was previously used for a large variety of conditions and this changed until this point where its use is highly restricted. Amphetamine, with the chemical formula alpha-methylphenethylamine, was discovered in 1910 and first synthesized by 1927. After being proven to reduce drug-induced anesthesia and produce arousal and insomnia, amphetamine racemic mix was registered by Smith, Kline and French in 1935. Amphetamine structure presents one chiral center and it exists in the form of dextro- and levo-isomers. The first product of Smith, Kline and French was approved by the FDA on 1976.
During World War II, amphetamine was used to promote wakefulness in the soldiers. This use derived into a large overproduction of amphetamine and all the surplus after the war finalized ended up in the black market, producing the initiation of the illicit abuse.

Indications

Amphetamine is indicated for the treatment of attention-deficit/hyperactivity disorders (ADHD) as well as for the treatment of central nervous system disorders such as narcolepsy.
ADHD is a complex disorder associated with the substantial heterogeneity in etiology, clinical presentation, and treatment outcome. ADHD comes from a complex interplay between interdependent genetic and non-genetic factors which cause complex mental disorders in children and teenagers.
On the other hand, narcolepsy is a chronic sleep disorder typically resenting during adolescence and characterized by excessive daytime sleepiness.
Amphetamine is also being used nowadays off-label for the treatment of obesity, depression and chronic pain.

Definition

ChEBI: 1-phenylpropan-2-amine is a primary amine that is isopropylamine in which a hydrogen attached to one of the methyl groups has been replaced by a phenyl group.

brand name

Benzadrine (SmithKline Beecham);Amfetamin;Amfetasul;Amphamed;Amphedrine;Bifentamin;Dexamin;Dexatrine;Isoamyn;Norphedrane;Novydrinene;Obesitab;Obetrol;Oktadrin;Perduretas anfetamina;Sympatedrin;Sympatina;Synatan;Wekamine.

World Health Organization (WHO)

Amfetamine and its derivatives are potent central stimulants. Use of amfetamines has widely been discouraged due to abuse of their euphoric effect and their limited field of usefulness. Amfetamines have a place in the treatment of narcolepsy and in hyperkinetic syndrome in children. However, they are no longer recommended for use in obesity or depressive illness. Amfetamine is controlled under Schedule II of the 1971 Convention on Psychotropic Substances. (Reference: (UNCPS2) United Nations Convention on Psychotropic Substances (II), , , 1971)

General Description

Colored liquid with an amine odor. Used as a pharmaceutical, a central nervous system stimulant.

Reactivity Profile

Amines, such as D/L-AMPHETAMINE HYDROCHLORIDE, are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.

Hazard

Flammable, moderate fire risk. Basis of a group of hallucinogenic (habit-forming) drugs that affect the central nervous system. Sale and use restricted to physicians. Production limited by law.

Health Hazard

D/L-AMPHETAMINE HYDROCHLORIDE is classified as extremely hazardous. Probable lethal dose in humans is 5-50 mg/kg or 7 drops to 1 teaspoon for a 70 kg (150 lb.) person. Habit forming drug which affects the central nervous system. Excessive use may lead to tolerance and physical dependence. Death is possible.

Fire Hazard

Dangerous when exposed to heat or flames. Upon decomposition, nitrogen oxides are emitted. Can react with oxidizing materials.

Pharmacokinetics

From its mechanism of action, it has been demonstrated that amphetamine augments the concentration of noradrenaline in the prefrontal cortex and dopamine in the striatum on a dose and time-dependent manner. The indistinct release of neurotransmitters which include adrenaline is known to produce cardiovascular side effects.
There are old reports of a cognitive enhancement related to the administration of amphetamine in which improvements in intelligence test scores were reported.
In ADHD, amphetamine has been largely showed to produce remarkable improvements in school performance, behavior, and demeanor. The effect was shown to be produced through both racemic forms and to this date, the use of racemic forms 3:1 (D:L) is very common. The therapeutic effect of amphetamine on serotonin does not seem to have a significant clinical effect on ADHD as observed on comparative studies with amphetamine and fenfluramine, a powerful serotonin releasing factor. However, the indirect effect on serotonin might have an effect on the depression and anxiety profile of ADHD.
Studies regarding the illicit use of amphetamine in which heavy consumers were studied proved the generation of a paranoid state which flagged this drug as a psychiatric danger compound. This observation was supported by the continuous reports of misuse in patients under depression.

Safety Profile

A deadly human poison by an unspecified route. An experimental poison by ingestion, subcutaneous, intraperitoneal, and intravenous routes. Experimental reproductive effects. Mutation data reported. A central nervous system stimulant. Overdoses cause hyperactivity, restlessness, insomnia, rapid pulse, rise in blood pressure, dilated pupils, dryness of the throat. Combustible when exposed to heat, flame, or oxidizers. When heated to decomposition it emits toxic fumes of NO,. To fight fire, use CO2, dry chemical, alcohol foam, water mist, fog. See other benzedrine entries.

Potential Exposure

Amphetamine is used as a pharmaceutical. It is a CNS stimulant.

First aid

If this chemical gets into the eyes, remove anycontact lenses at once and irrigate immediately for at least15 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts theskin, remove contaminated clothing and wash immediatelywith soap and water. Seek medical attention immediately. Ifthis chemical has been inhaled, remove from exposure,begin rescue breathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPR ifheart action has stopped. Transfer promptly to a medicalfacility. When this chemical has been swallowed, get medical attention. Give large quantities of water and inducevomiting. Do not make an unconscious person vomit.

Environmental Fate

Amphetamines are indirect acting sympathomimetics, producing their effects by inhibiting the transporters of dopamine, norepinephrine, and serotonin at the presynaptic nerve terminal. This increases the release of norepinephrine, dopamine, and serotonin and increased norepinephrine levels at central synapses, which further stimulates alpha and beta receptors. Some amphetamines also inhibit monoamine oxidase, preventing the breakdownof catecholamines. Thesemechanisms combine to produce the sympathomimetic and central nervous system (CNS) effects seen with amphetamine abuse.

Metabolism

Amphetamine is known to be metabolized by the liver under the action of the CYP2D6. The metabolic pathway of amphetamine is mainly defined by aromatic hydroxylation, aliphatic hydroxylation, and n-dealkylation. The formed metabolites in this pathway are 4-hydroxyamphetamine, 4-hydroxynorephedrine, hippuric acid, benzoic acid, benzyl methyl ketone, and p-hydroxyamphetamine which is known to be a potent hallucinogen. However, a significant part of the original compound remains unchanged.

storage

Color Code—Blue: Health Hazard/Poison: Store ina secure poison location. Prior to working with this chemicalyou should be trained on its proper handling and storage.Store in a refrigerator or a cool, dry place.

Shipping

UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required.

Toxicity evaluation

Amphetamine is a clear to colorless liquid in freebase or white crystalline substance as a salt. As a liquid it slowly volatilizes and has a characteristic amine odor. Amphetamine base is slightly soluble in water, soluble in alcohol and ether. The melting point of amphetamine is 300
C with some decomposition occurring.

Incompatibilities

Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides.

Waste Disposal

It is inappropriate and possibly dangerous to the environment to dispose of expired or waste pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double-bagged in plastic, discard in trash. Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. All federal, state, and local environmental regulations must be observed.