Absorption, Distribution and Excretion
Amphetamine is well absorbed in the intestine. As it is a weakly alkaline substance, the more alkaline the environment, the higher the proportion of the drug existing in its lipid-soluble form, and the easier it is to absorb through lipid-rich cell membranes. Peak plasma concentrations are reached 1-3 hours after oral administration and approximately 15 minutes after injection, with a bioavailability exceeding 75%. Amphetamine is usually completely absorbed within 4-6 hours. Amphetamine is primarily excreted in the urine, with approximately 40% of the excreted dose existing unchanged. Within 3 days of oral administration, approximately 90% of the administered dose is excreted. The elimination rate of amphetamine is highly dependent on urine pH; acidic pH promotes excretion, while alkaline pH reduces it. The reported volume of distribution of amphetamine is up to 4 L/kg. The normal clearance is 0.7 L/h/kg. The clearance rate is significantly reduced in patients with renal insufficiency, reaching 0.4 L/h/kg. Children: Children clear amphetamine faster than adults. Breast milk: Amphetamine is secreted into human breast milk. Amphetamine is readily absorbed from the gastrointestinal tract, and its effects can last for 4–24 hours. Amphetamine is distributed in most body tissues, with higher concentrations in the brain and cerebrospinal fluid. Amphetamine can be detected in urine about 3 hours after oral administration. The urinary excretion of amphetamine is affected by pH, with increased excretion in acidic urine. After oral administration of racemic amphetamine, the excretion of the two isomers is roughly equal in the first 12 hours; after 12 hours, the excretion of the d-isomer continues to decrease. The content of amphetamine has been measured in human sweat, with median ranges of 15.5 ng per tablet (6.5–40.5 ng for low doses) and 53.8 ng per tablet (34.0–83.4 ng for high doses) (1). For more complete data on the absorption, distribution, and excretion of amphetamines (7 types), please visit the HSDB record page. Metabolism/Metabolites Amphetamines are known to be metabolized in the liver by CYP2D6. The metabolic pathway of amphetamines mainly involves aromatic hydroxylation, aliphatic hydroxylation, and N-dealkylation. Metabolites produced by this pathway include 4-hydroxyamphetamine, 4-hydroxynorephedrine, hippuric acid, benzoic acid, benzylmethyl ketone, and p-hydroxyamphetamine (a potent hallucinogen). However, a significant portion of the original drug remains unchanged. Amphetamines are metabolized in the liver via aromatic hydroxylation, N-dealkylation, and deamination. Although the enzymes involved in amphetamine metabolism are not fully understood, cytochrome P450 (CYP-450) 2D6 is known to be involved in the formation of 4-hydroxyamphetamine. Due to the genetic polymorphism of CYP2D6, amphetamine metabolism may vary across populations. Metabolic pathways of amphetamine include aromatic hydroxylation, aliphatic hydroxylation, and N-dealkylation, which produce 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. Liver Half-life: 10 hours

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Biological Half-life
The half-life of amphetamine is highly dependent on its isomers. It has been reported that the half-life of dextroamphetamine is approximately 9–11 hours, while that of levoamphetamine is approximately 11–14 hours. Urine pH affects this pharmacokinetic parameter, with a half-life of 7 hours in acidic urine and 34 hours in alkaline urine.
The biological half-life is 10–13 hours in adults and 9–11 hours in children.

Toxicity Summary
Identification and Uses: Amphetamine is a colorless liquid with a characteristic amine odor (similar to geranium leaves) and a pungent taste. Its indications are as follows: Psychostimulant: Approved indications: Narcolepsy; ADHD in children (as an adjunct to psychological, educational, and social interventions). This drug is often abused to improve athletic performance. Oral or injectable abuse is extremely common. Human Exposure and Toxicity: Major risks include: acute central nervous system (CNS) excitation, cardiotoxicity (which can lead to tachycardia, arrhythmias, hypertension, and cardiovascular failure). It has a high degree of dependence and abuse risk. Cardiovascular effects include: palpitations, chest pain, tachycardia, arrhythmias, and hypertension; severe poisoning can lead to cardiovascular failure, as well as myocardial ischemia, infarction, and ventricular dysfunction. Central nervous system effects include: central nervous system excitation, tremor, restlessness, anxiety, insomnia, hyperkinesis, headache, convulsions, coma, and hyperreflexia. Stroke and cerebrovascular disease have been observed. Gastrointestinal effects include vomiting, diarrhea, and cramps. Long-term methamphetamine abuse can lead to acute transient ischemic colitis. Genitourinary effects: Increased bladder sphincter tone may cause difficulty urinating, urinary hesitation, and acute urinary retention. Dehydration or rhabdomyolysis can lead to secondary renal failure. Renal ischemia may occur. Transient hyperthyroidism may occur. Increased metabolism and muscle activity may lead to hyperventilation and hyperthermia. Weight loss is common with long-term use. Hypokalemia and hyperkalemia have been reported. Dehydration is common. Fascination and muscle rigidity may occur. Rhabdomyolysis is a significant consequence of severe amphetamine poisoning. Typical symptoms include agitation, confusion, elevated mood, increased arousal, talkativeness, irritability, and panic attacks. Long-term abuse can lead to delusions and paranoia. Abrupt cessation of long-term use can cause withdrawal syndrome. Amphetamines appear to act primarily or entirely on the central nervous system by stimulating the release of biogenic amines, particularly norepinephrine and dopamine, from nerve endings. It may also slow the metabolism of catecholamines by inhibiting monoamine oxidase. Children appear to be more susceptible than adults and are less likely to develop tolerance. Medical use of amphetamines does not pose a significant risk of birth defects in the fetus. Amphetamines are generally not considered teratogenic in humans. Newborns may experience mild withdrawal symptoms, but few follow-up studies in infants have not found long-term sequelae. Illicit use or abuse of amphetamines by pregnant women poses significant risks to the fetus and newborn, including intrauterine growth retardation, premature birth, and increased maternal and infant morbidity. However, brain damage in newborns exposed to amphetamines in utero appears to be directly related to the vasoconstrictive properties of amphetamines. One study investigated 65 children whose mothers were addicted to amphetamines during pregnancy (at least in the first trimester). These children were within the normal range in terms of intelligence, psychological function, growth and development, and physical health at age eight, but those exposed to amphetamines throughout pregnancy tended to be more aggressive. Animal studies: Retinal toxicity tests were negative; dogs given 10 mg/kg daily for three months occasionally showed mild fundus pallor, but no retinal histological changes were observed. A study investigated the behavioral effects of dextromethorphan in 17 adult cats. Subcutaneous doses of amphetamine were 0.1, 0.5, 1.0, and 5.0 mg/kg. Amphetamine administration caused dose-dependent reductions in activity, with higher doses showing more significant reductions. Furthermore, stereotyped behavioral patterns, such as rhythmic bilateral slow head movements, indifference to the environment, and a dose-dependent increase in respiratory rate, were observed in amphetamine-treated cats. Amphetamine can damage cerebral arteries in experimental animal models. Ecotoxicity studies: In the freshwater bivalves Dreissena polymorpha, the antioxidant activity of amphetamines at the highest tested concentration (5000 ng/L) exhibited a bell-shaped trend, indicating excessive reactive oxygen species production leading to oxidative damage. This was confirmed by a significant increase in protein carbonylation and DNA fragmentation. Amphetamines stimulate the release of norepinephrine from central adrenergic receptors. At high doses, amphetamines promote dopamine release from the limbic system and the substantia nigra-striatal dopamine system. Amphetamines may also directly stimulate central serotonin (5-HT) receptors and inhibit monoamine oxidase (MAO). Peripherally, amphetamines are thought to promote norepinephrine release by acting on adrenergic nerve endings and α and β receptors. Regulation of the serotonergic pathway may contribute to its sedative effect. The drug interacts with VMAT enzymes, enhancing the release of dopamine (DA) and 5-HT from vesicles. It may also directly lead to the reversal of DAT and SERT.

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Toxicity Data
LD50: 180 mg/kg (subcutaneous injection, rat) (A308)Interactions
Amphetamine inhibits the hypotensive effect of veratrum alkaloids.

In propoxyphene overdose, the central nervous system excitatory effect of amphetamine is enhanced, potentially leading to fatal seizures.

Amphetamine may delay the intestinal absorption of phenytoin; co-administration with phenytoin may produce a synergistic anticonvulsant effect.

Amphetamine may delay the intestinal absorption of phenobarbital. Co-administration with phenobarbital may produce a synergistic anticonvulsant effect.

For more complete data on interactions of amphetamines (24 in total), please visit the HSDB record page.

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Non-human toxicity values
Rat intraperitoneal injection LD50: 125 mg/kg
Rat subcutaneous injection LD50: 39 mg/kg
Mouse oral LD50: 22 mg/kg
Mouse intraperitoneal injection LD50: 16 mg/kg
For more complete non-human toxicity data for amphetamines (6 in total), please visit the HSDB record page.

Therapeutic Uses
Adrenergic drugs; Adrenergic reuptake inhibitors; Central nervous system stimulants; Dopaminergic drugs; Dopamine reuptake inhibitors; Sympathomimetic drugs.
/Clinical Trials/ ClinicalTrials.gov is a registry and results database that tracks human clinical studies funded by public and private institutions worldwide. The website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each record on ClinicalTrials.gov provides summary information on the study protocol, including: the disease or condition; the intervention (e.g., the medical product, behavior, or procedure under investigation); the title, description, and design of the study; participation requirements (eligibility criteria); the location of the study; contact information for the study location; and links to relevant information on other health websites, such as the NLM's MedlinePlus (for patient health information) and PubMed (for citations and abstracts of academic articles in the medical field). The database contains amphetamines.
Evekeo (Amphetamine Sulfate Tablets, USP) is indicated for: 1. Narcolepsy; 2. Attention Deficit Hyperactivity Disorder (ADHD) as part of a comprehensive treatment program that typically includes other remedies (psychological, educational, and social) to stabilize the child’s behavioral syndrome. This syndrome is characterized by the presence of a group of developmentally incoordinating symptoms: moderate to severe inattention, short attention span, hyperactivity, mood instability, and impulsivity. If these symptoms are relatively short-lived, a definitive diagnosis of the syndrome should not be made. Non-localizing (soft) neurological signs, learning disabilities, and EEG abnormalities may or may not be present, therefore a diagnosis of central nervous system dysfunction may or may not be necessary. 3. Exogenous obesity: as a short-term (several weeks) adjunctive therapy for calorie-restricted weight loss programs in patients who have not responded to other therapies (e.g., repeated dieting, group programs, and other medications). /US Product Label Includes/
Veterinary: Used to relieve anesthetic overdose, particularly barbiturate overdose. Enhances responsiveness to external stimuli, such as depression in dairy cows and postpartum hypocalcemia. It may be effective in some cases of encephalomyelitis (equine), epilepsy (cow), or ADHD.

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Drug Warning
/Black Box Warning/ Amphetamines have a high potential for abuse. Long-term use of amphetamines can lead to drug dependence and must be avoided. Special attention should be paid to the possibility that patients may obtain amphetamines for non-therapeutic purposes or distribute them to others, and prescription or dispensing should be done with caution. Abuse of amphetamines can lead to sudden death and serious adverse cardiovascular events.
Amphetamines are excreted into breast milk at concentrations 3-7 times higher than maternal blood concentrations. A decision should be made regarding whether to discontinue breastfeeding or to discontinue the medication.
Amphetamines should only be used during pregnancy if the potential benefits outweigh the potential risks to the fetus. Whether the potential benefits of amphetamine use during pregnancy outweigh the potential risks remains questionable. Infants born to women dependent on amphetamines have an increased risk of premature birth, low birth weight, and withdrawal symptoms (e.g., irritability, fatigue, agitation).
Adverse reactions to amphetamine may include: nervousness, insomnia, irritability, talkativeness, altered libido, dizziness, headache, increased activity, chills, pallor or flushing, blurred vision, dilated pupils, and hyperexcitability. Patients taking amphetamine have reported symptoms such as increased motor or vocal tics, Tourette syndrome, movement disorders, seizures, euphoria, restlessness, mood swings, and impotence. Psychotic episodes are extremely rare in patients taking the recommended dose of amphetamine.
For more complete data on drug warnings for amphetamine (21 in total), please visit the HSDB record page.
Pharmacodynamics
Based on its mechanism of action, amphetamine has been shown to increase the concentrations of norepinephrine in the prefrontal cortex and dopamine in the striatum in a dose- and time-dependent manner. Disordered release of neurotransmitters, including adrenaline, is known to produce cardiovascular side effects. Early reports indicated that amphetamines could enhance cognitive abilities, with reports of improved IQ test scores. In the treatment of attention deficit hyperactivity disorder (ADHD), amphetamines have been shown to significantly improve patients' academic performance, behavior, and mannerisms. Studies have shown that both racemic and mutagenic forms of amphetamine produce this effect, and to date, the 3:1 (D:L) racemic mixture remains very common. The therapeutic effect of amphetamines on serotonin does not appear to have a significant clinical efficacy for ADHD, consistent with comparative studies of amphetamines and fenfluramine (a potent serotonin-releasing factor). However, the indirect effects of amphetamines on serotonin may influence depressive and anxiety symptoms in ADHD patients. Studies on the illicit use of amphetamines, particularly those involving heavy users, have confirmed that amphetamines can induce delusional states, indicating a psychological danger posed by the drug. Cases of amphetamine abuse by patients with depression also corroborate this view.

C9H13N

135.20622

135.104

300-62-9

60-13-9 (sulfate); 300-62-9; 2706-50-5 (HCl);

3007

Mobile liquid
Colorless, volatile liquid

1.8

1

1

2

10

84.7

0

KWTSXDURSIMDCE-UHFFFAOYSA-N

InChI=1S/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3

alpha-Methylphenethylamine

Amphetamine NSC-27159 NSC27159 NSC 27159

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)