α-Methylphenethylamin

Stimulant

Pharmaceutical

DEA NFLIS-Drug Category -> Phenethylamines (Amphetamines) (S)

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

Pharmaceuticals -> Illicit drugs

Pharmaceuticals

log Kow = 1.76

1.8

1.76

Amine odor

Characteristic strong odor

Acrid, burning taste

Slightly burning taste

0.913 at 77 °F (EPA, 1998) - Less dense than water; will float

0.936 g/cu cm at 25 °C

Mobile liquid

Colorless, volatile liquid

Moderate solubility

Sparingly soluble in water (1:50)

Slightly soluble in water

Readily sol in acids

Slightly soluble inethyl ether; soluble in ethanol and chloroform

1.74e+00 g/L

80 °F (EPA, 1998)

</= 100 °C

Breast Feeding; Lactation; Milk, Human; Adrenergic Agents; Central Nervous System Stimulants; Dopamine Agents; Sympathomimetics; Wakefulness-Promoting Agents

Breast Feeding; Lactation; Milk, Human; Adrenergic Agents; Central Nervous System Stimulants; Dopamine Agents; Sympathomimetics; Wakefulness-Promoting Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

392 to 397 °F at 760 mmHg (EPA, 1998)

200-203 °C at 760 mm Hg

Danger

H226 (95.1%): Flammable liquid and vapor [Warning Flammable liquids]

P210, P233, P240, P241, P242, P243, P264, P270, P280, P301+P316, P303+P361+P353, P321, P330, P370+P378, P403+P235, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 41 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H225: Highly Flammable liquid and vapor [Danger Flammable liquids]

It 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. (EPA, 1998)

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including amphetamine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Amphetamine sulfate/

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including amphetamine aspartate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Amphetamine aspartate/

Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... (d) Stimulants. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a stimulant effect on the central nervous system: Amphetamine, its salts, optical isomers, and salts of its optical isomers (DEA Code Number: 1100) is included on this list. /Amphetamine, its salts, optical isomers, and salts of its optical isomers/

Johnston, L. D. et al; Monitoring the Future, National Survey Results on Drug Use: 1975-2014: Overview, key findings on adolescent drug use. Ann Arbor: Institute for Social Research, The University of Michigan.[Available from, as of April 20, 2016: http://www.monitoringthefuture.org/pubs/monographs/mtf-overview2014.pdf]

Caldwell J, Sever PS; Clin Pharmacol Ther 16 (10): 625-38 (1974). Pharmacology, metabolism, tolerance & manifestation of abuse of amphetamines, cocaine & lysergic acid diethylamide are reviewed.

DHHS/NIDA; Research Monograph Series 52: Testing Drugs for Physical Dependence Potential and Abuse Liability (1984) DHHS Pub No. (ADM)87-1332

DHHS/NIDA; Research Monograph Series 54: Mechanisms of Tolerance and Dependence (1984) DHHS Pub No. (ADM)88-1330

For more Special Reports (Complete) data for AMPHETAMINE (11 total), please visit the HSDB record page.

Amines, such as AMPHETAMINE, 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.

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Amphetamine is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 1,000 lbs.

Signs and Symptoms of Amphetamine Exposure: Signs and symptoms of acute amphetamine exposure include the following: headache, flushing or pallor, dry mouth, metallic taste, loss of appetite, abdominal cramps, nausea, vomiting, diarrhea, difficulty urinating, chills or fever, restlessness, dizziness, tremors, and hyperactive reflexes. Mood and behavioral changes may include irritability, apprehensiveness, talkativeness, and confusion. Convulsions and coma may also occur. Cardiovascular signs include hypertension (high blood pressure) and tachycardia (rapid heart beat). Cardiovascular collapse may occur in cases of extreme intoxication.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Recommended storage temperature -20 °C

ACCIDENTAL RELEASE MEASURES. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapours accumulating to form explosive concentrations. Vapours can accumulate in low areas.; Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.; Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations.

(Non-Specific -- Drugs, n.o.s.) Keep unnecessary people away; isolate hazard area and deny entry. Stay upwind; keep out of low areas. Shut off ignition sources; no flares, smoking or flames in hazard area. Keep combustibles (wood, paper, oil, etc.) away from spilled material. Do not touch spilled material.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. 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 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.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid inhalation of vapour or mist. Use explosion-proof equipment.Keep away from sources of ignition - No smoking.Take measures to prevent the build up of electrostatic charge.

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Body Protection: Complete suit protecting against chemicals, Flame retardant antistatic protective clothing., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Skin protection: Handle with gloves.

Eye/face protection: Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Amphetamines inhibit the hypotensive effect of veratrum alkaloids.

In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.

Amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant action.

Amphetamines may delay intestinal absorption of Phenobarbital. Co-administration of phenobarbital may produce a synergistic anticonvulsant action.

For more Interactions (Complete) data for AMPHETAMINE (24 total), please visit the HSDB record page.

Prolonged use may cause hallucinations and intense paranoia. Amphetamines are psychologically addictive. Users who stop using them report that they experience various mood problems such as aggression and anxiety and intense cravings for the drugs. Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 760(SRC), determined from a structure estimation method(2), indicates that amphetamine is expected to have low mobility in soil(SRC). The pKa of amphetamine is 10.13(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Amphetamine has a low vapor pressure of 0.24 mm Hg(5) and exists as a liquid under environmental conditions; therefore, amphetamine may volatilize from dry soil. An 76% degradation in 15 days using a river water/sediment bioreator(6) suggests that biodegradation may be an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 760(SRC), determined from a structure estimation method(2), indicates that amphetamine is expected to adsorb to suspended solids and sediment(SRC). A pKa of 10.24(3) indicates amphetamine will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water or moist soil surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 7(SRC), from its log Kow of 1.76(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). An 85% degradation in 15 days using a river water bioreactor(6) suggests that biodegradation may be an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), amphetamine, which has a vapor pressure of 0.24 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase amphetamine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 3 hrs(SRC), calculated from its rate constant of 4.9X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Amphetamine does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Reports exist of slowing growth velocity and reduction in adult height in patients who took stimulants as children, with an average adult height deficit of 4.7 cm among patients who consistently took the medication. This stunted growth appears to be primarily a consequence of reduced appetite and caloric intake associated with stimulant medications.

The drug is concentrated in human milk. /From Table 2/

Amphetamine readily passes into and is concentrated in breast milk.

IDENTIFICATION AND USE: Amphetamine is a colorless liquid with characteristic amine odor (similar to geranium leaves) and an acrid taste. It is used for the following indications: Psychostimulant: Accepted indications: Narcolepsy; Hyperkinetic states in children (as an adjunct to psychological, educational and social measures). The drug is misused for performance enhancement. Abuse either orally or by injection is extremely common. HUMAN EXPOSURE AND TOXICITY: Main risks include: acute central nervous system (CNS) stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension and cardiovascular collapse. High risk of dependency and abuse. Cardiovascular effects include: palpitation, chest pain, tachycardia, arrhythmias and hypertension; cardiovascular collapse can occur in severe poisoning, as well as, myocardial ischemia, infarction and ventricular dysfunction. CNS effects include: stimulation of CNS, tremor, restlessness, agitation, insomnia, increased motor activity, headache, convulsions, coma and hyperreflexia. Stroke and cerebral vasculitis have been observed. Gastrointestinal effects include: vomiting, diarrhea and cramps. Acute transient ischemic colitis has occurred with chronic methamphetamine abuse. Genitourinary effects: increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. Renal failure can occur secondary to dehydration or rhabdomyolysis. Renal ischemia may be noted. Transient hyperthyroxinemia may be noted. Increased metabolic and muscular activity may result in hyperventilation and hyperthermia. Weight loss is common with chronic use. Hypo- and hyperkalemia have been reported. Dehydration is common. Fasciculations and rigidity may be noted. Rhabdomyolysis is an important consequence of severe amphetamine poisoning. Agitation, confusion, mood elevation, increased wakefulness, talkativeness, irritability and panic attacks are typical. Chronic abuse can cause delusions and paranoia. A withdrawal syndrome occurs after abrupt cessation following chronic use. Amphetamine appears to exert most or all of its effect in the CNS by causing release of biogenic amines, especially norepinephrine and dopamine, from storage sites in nerve terminals. It may also slow down catecholamine metabolism by inhibiting monoamine oxidase. Children appear to be more susceptible than adults and are less likely to have developed tolerance. The use of amphetamine for medical indications does not pose a significant risk to the fetus for congenital anomalies. Amphetamines generally do not appear to be human teratogens. Mild withdrawal symptoms may be observed in the newborn, but the few studies of infant follow-up have not shown long-term sequelae. Illicit maternal use or abuse of amphetamine presents a significant risk to the fetus and newborn, including intrauterine growth retardation, premature delivery and the potential for increased maternal, fetal and neonatal morbidity. However, cerebral injuries occurring in newborns exposed in utero appear to be directly related to the vasoconstrictive properties of amphetamines. 65 children whose mothers were addicted to amphetamine during pregnancy, at least during the first trimester, were studied. Intelligence, psychological function, growth, and physical health were all within the normal range at eight years, but those children exposed throughout pregnancy tended to be more aggressive. ANIMAL STUDIES: Testing for toxicity to the retina has been negative; 10 mg/kg given daily to dogs for three months caused occasional slight ophthalmoscopic appearance of blanching of the fundus, but no histologic change in the retina. The behavioral effects of d-amphetamine administration were studied in 17 adult cats. The doses of amphetamine administered were 0.1, 0.5, 1.0 and 5.0 mg/kg sc. Amphetamine administration induced a dose-dependent hypomotility, which was marked with the higher doses. In addition, rhythmic, bilateral slow movements of the head as a mode of stereotype, indifference to the environment and dose-dependent incr in respiratory rate were observed in amphetamine-treated cats. Amphetamine damages cerebral arteries in experimental animal models. ECOTOXICITY STUDIES: In the freshwater bivalve Dreissena polymorpha the bell-shaped trend of antioxidants showed at the highest tested amphetamine concentration (5000 ng/L) suggested an overproduction of reactive oxygen species, leading to oxidative damage, as confirmed by the significant increase of protein carbonylation and DNA fragmentation.

Due to their ability to produce powerful euphoric effects, amphetamines are common drugs of abuse. All major drugs of abuse increase dopamine concentrations in the mesolimbic pathway, but amphetamines, because of their direct effects on DAT and VMAT2, can increase dopamine concentrations far beyond the concentrations seen for natural rewarding stimuli. Chronic exposure to amphetamine, particularly methamphetamine, at recreational doses has shown to destroy dopaminergic terminals in the striatum through a variety of mechanisms, including oxidative stress and excitotoxicity. The resultant blunting of the physiological dopamine response can further potentiate abuse.

Amphetamines stimulate the release of norepinephrine from central adrenergic receptors. At higher dosages, they cause release of dopamine from the mesocorticolimbic system and the nigrostriatal dopamine systems. Amphetamine may also act as a direct agonist on central 5-HT receptors and may inhibit monoamine oxidase (MAO). In the periphery, amphetamines are believed to cause the release of noradrenaline by acting on the adrenergic nerve terminals and alpha- and beta-receptors. Modulation of serotonergic pathways may contribute to the calming affect. The drug interacts with VMAT enzymes to enhance release of DA and 5-HT from vesicles. It may also directly cause the reversal of DAT and SERT.

/AQUATIC SPECIES/ Illicit drugs have been recognized as emerging aquatic pollutants due to their presence in aquatic ecosystems up to ug/L level. Among these, the synthetic psycho-stimulant drug amphetamine (AMPH) is commonly found in both surface and wastewaters worldwide. Even though the environmental occurrence of AMPH is well-known, the information on its toxicity towards non-target freshwater organisms is completely lacking. This study investigated the imbalance of the oxidative status and both oxidative and genetic damage induced by a 14-day exposure to two concentrations (500 ng/L and 5000 ng/L) of AMPH on the freshwater bivalve Dreissena polymorpha by the application of a biomarker suite. ...The activity of antioxidant enzymes (SOD, CAT and GPx), the phase II detoxifying enzyme GST, the lipid peroxidation level (LPO) and protein carbonyl content (PCC), as well as primary (Single Cell Gel Electrophoresis assay) and fixed (DNA diffusion assay and Micronucleus test) genetic damage /was examined/. /The/ results showed that a current ... AMPH concentration (500 ng/L) did /not/ ...cause notable imbalances in enzymatic activities, ... /or/ oxidative and genetic damage to cellular macromolecules. In contrast, the bell-shaped trend of antioxidants showed at the highest tested concentration (5000 ng/L) suggested an overproduction of reactive oxygen species, leading to oxidative damage, as confirmed by the significant increase of protein carbonylation and DNA fragmentation.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. /DL-Amphetamine sulfate/[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=60-13-9]

Amphetamine was present at an average loading rate of 114 and <10 g/day in influent and effluent, respectively, collected from a wastewater treatment plant in conjunction with a US major sporting event (National Football League's Super Bowl). Non-event loadings were 125 and <10 g/day(1). The compound was detected at a mean concentration of 148.0 ng/L (range 3.3-6640 ng/L; 93% of 14 samples positive) in influent sewage samples from the Ebro River Basin, Spain, sampled in October 2007 and July 2008. A median concentration of 25.7 ng/L (range 0.5-7.6 ng/L; 36% of 14 samples positive) was reported for effluent samples(2).

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including amphetamine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Amphetamine sulfate/

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including amphetamine aspartate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Amphetamine aspartate/

Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... (d) Stimulants. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a stimulant effect on the central nervous system: Amphetamine, its salts, optical isomers, and salts of its optical isomers (DEA Code Number: 1100) is included on this list. /Amphetamine, its salts, optical isomers, and salts of its optical isomers/

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Amphetamine is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 1,000 lbs.

N - Nervous system

QN - Nervous system

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.

Amphetamine's structure closely resembles catecholamine neurotransmitters, characterized primarily by a long planar conformation, an aromatic ring, and nitrogen in the aryl side chain. Like endogenous catecholamines, amphetamine is actively transported into presynaptic nerve terminals via monoamine reuptake transporters, which require association with two sodium ions and one chloride ion. Because amphetamine acts as a competitive substrate, increased concentrations lead to greater internalization of amphetamine. Once in the presynaptic terminal, amphetamine competes for storage in VMAT2 (Vesicular Monoamine Transporter 2), displacing other monoamines. This action induces the release of neurotransmitters into the synapse through a process known as reverse transport. The d-isomer is approximately fourfold more potent than the $l$-isomer in promoting dopamine release via this mechanism. The mechanism of action is further complemented by the inhibition of both monoamine reuptake and monoamine oxidase (MAO), which act synergistically to significantly elevate monoamine concentrations. Amphetamine does not act as a direct inhibitor but rather as a competitive substrate, classifying it as a weak dopamine reuptake inhibitor, a moderate noradrenaline reuptake inhibitor, and a very weak serotonin reuptake inhibitor. Consequently, the l-isomer exhibits significantly lower potency in this specific action. Amphetamine acts as a weak inhibitor of the mitochondrial-bound enzyme MAO, the catalytic enzyme responsible for degrading excess neurotransmitters. Although this mechanism is often considered minor due to its weak inhibitory nature, it remains a component of amphetamine's overall action. Amphetamine is a modulator of glutamatergic neurotransmission, primarily via its action on the dopamine system. The mass release of dopamine caused by amphetamine subsequently signals to the glutamatergic system, leading to long-lasting changes in synaptic plasticity. Amphetamine's entry into dopamine neurons triggers the endocytosis of the excitatory amino acid transporter EAAT3, reducing glutamate clearance and potentiating excitatory synaptic responses mediated by ionotropic receptors. Chronic exposure also alters receptor composition, such as the downregulation of the NMDA receptor NR2B subunit in the striatum, which is a key molecular change underlying behavioral sensitization to the drug.

Inactivation of sympathomimetic noncatecholamines largely depends on breakdown by monoamine oxidase and since substitution of an alkyl group for hydrogen on the a-carbon atom blocks enzymatic inactivation of the amino group, the duration of action of noncatecholamines (but not of catecholamines, which are inactivated largely by a different mechanism) is prolonged by a-substitution. The absence of a hydroxyl group on the aromatic ring of amphetamine reduces inactivation of the drug in the GI tract and the amphetamines are active following oral administration.

The half-life of amphetamine highly depends on the isomer. For d-amphetamine, the reported half-life is of approximately 9-11 hours while for l-amphetamine the half-life is reported to be of 11-14 hours. The urine pH can modify this pharmacokinetic parameter which can vary from 7 hours in acid urine to 34 hours for alkaline urine.

Biological half-life is between 10-13 hr in adults and 9-11 hr in children.

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.

Amphetamine is metabolized in the liver by aromatic hyroxylation, N-dealkylation, and deamination. Although the enzymes involved in amphetamine metabolism have not been clearly defined, cytochrome P450 (CYP-450) 2D6 is known to be involved with formation of 4-hydroxy-amphetamine. Because CYP2D6 is genetically polymorphic, population variations in amphetamine metabolism are a posibility.

Metabolism that results in aromatic hydroxylation, aliphatic hydroxylation, and n-dealkylation of amphetamines can give rise to active metabolites such as the potent hallucinogen p-hydroxyamphetamine. Other metabolic pathways, including deamination and subsequent side chain oxidation, produce inactive amphetamine derivatives.

Amphetamine is a known human metabolite of Fenproporex.

Hepatic Half Life: 10 hours

CK833KGX7E

AMPHETAMINE

Established Pharmacologic Class [EPC] - Central Nervous System Stimulant

Physiologic Effects [PE] - Central Nervous System Stimulation

Amphetamine is a Central Nervous System Stimulant. The physiologic effect of amphetamine is by means of Central Nervous System Stimulation.

AMPHETAMINE

A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here.

Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters.

Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.

Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters.

Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.

Drugs that block the transport of DOPAMINE into axon terminals or into storage vesicles within terminals. Most of the ADRENERGIC UPTAKE INHIBITORS also inhibit dopamine uptake.

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.

The elimination of amphetamine is mainly via the urine from which about 40% of the excreted dose is found as unchanged amphetamine. About 90% of the administered amphetamine is eliminated 3 days after oral administration. The rate of elimination of amphetamine highly depends on the urine pH in which acidic pH will produce a higher excretion of amphetamine and basic pH produces a lower excretion.

Amphetamine is reported to have a high volume of distribution of 4 L/kg.

The reported normal clearance rate is of 0.7 L.h/kg. This clearance has been shown to get significantly reduced in patients with renal impairment reaching a value of 0.4 L.h/kg.

Children: Children eliminated amphetamine faster than adults.

/MILK/ Amphetamines are excreted in human milk.

MEDICATION (VET)

MEDICATION

Amphetamine, its salts, optical isomers, and salts of its optical isomers (DEA Code Number: 1100) are Schedule II controlled substances. /Amphetamine, its salts, optical isomers, and salts of its optical isomers/

Schedule II Controlled Substance: (A) The drug or other substance has a high potential for abuse; (B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions; and (C) Abuse of the drug or other substances may lead to severe psychological or physical dependence.

For more Uses (Complete) data for AMPHETAMINE (6 total), please visit the HSDB record page.

Use (kg) in USA (2002): 4820

Di(1-phenylisopropyl)formamide is a by-product in the Leuckart synthesis of N-formylamphetamine, which is a reaction precursor to illegally produced dl-amphetamine. Side reactions and incomplete conversions lead to a variety of impurities and intermediate products, including benzyl methyl ketone, dibenzyl ketone, formamide, formic acid, methylamine, N,N-dimethylamphetamine, N-formylamphetamine, di(1-fenylisopropyl)amine, benzylamine, and several pyrimidine, pyridine, and pyridone compounds. Analysis of street samples suggests that amphetamines may be present in as little as 60% of purported samples. These illicit drugs contain varying amt of phencyclidine, LSD, STP, cocaine, atropine, mescaline, strychnine, and adulterants (eg, cornstarch, maltose, lactose, magnesium silicate, quinine, fibrous material).

Amphetamine is prepared by treating phenylacetone with formic acid and ammonia under the Leuckart-Wallach conditions.

Preparation: Goggin, USA patent 2507468 (1950 to Clarke & Clarke) /Amphetamine phosphate/

Preparation: ... F. P. Nabenhauer, USA patent 1921424 (1933 to SK & F).

Phenylacetone + hydroxylamine sulphate (oxime formation/hydrogenation)

Oral: amphetamine sulfate tablets, 5 mg, 10 mg, Evekeo. /Amphetamine sulfate/

... Heroin-amphetamine ("poor man's speedball") combinations.

Table: Amphetamine Sulfate Combination Preparations [Table#4528]

Common street names: Bennies, Black Beauties, Crank, Ice, Speed, and Uppers.

Pharmaceuticals

Pharmaceuticals -> Anaesthetics -> Transformation products

Benzeneethanamine, .alpha.-methyl-: ACTIVE

Amphetamine, the racemic mixture of levo- and dextroamphetamine ...

Amphetamine is the prototype of a class of noncatecholamine compounds that produce strong CNS stimulation.

The illicit manufacture, trafficking, and abuse of amphetamine increased during 1988 after remaining relatively stable during the previous 4 years. /The highest number of seizures/ occured in the Dallas Field Division. The second highest number of seizures occurred in the Houston Field Division.

Manufacture is restricted in most countries.