Dextroamphetamine is the central nervous system (CNS) of stimulants and enfera amphetamine prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy disorder. It is also used as an athletic performance and cognitive enhancer, and recreation as an aphrodisiac and euphoria. Dextroamphetamine is also used by military air, tanks, and special forces as a 'go-pill' during missions that trigger fatigues such as night-time bombing missions or extended combat operations.
Amphetamine molecules exist as two enantiomers, levoamphetamine and dextroamphetamine. Dextroamphetamine is dextrorotatori, or 'right-hand' enastomer, and shows a more noticeable effect on CNS than levoamphetamine. Pharmaceutical dextroamphetamine sulfate is available both as brand name and generic drug in various dosage forms. Dextroamphetamine is sometimes prescribed as an inactive lisdexamfetamine dimesylate prodrug, converted to dextroamphetamine after absorption.
Dextroamphetamine, like other amphetamines, stimulates its stimulating effects through several different actions: inhibiting or reversing transporter proteins for monoamine neurotransmitters (ie serotonin transporters, norepinephrine and dopamine) either via trace 1 (TAAR1) or in independent mode TAAR1 high cytosolic concentrations of monoamine neurotransmitters and release these neurotransmitters from synaptic vesicles via vesicular monoamine transporter 2. It also shares many chemical and pharmacological properties with human trace amines, especially phenethylamine and N -methylphenethylamine , the latter being the isomer of amphetamines produced in the human body.
Video Dextroamphetamine
Usage
Medical
Dextroamphetamine is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy (sleep disorder), and is sometimes prescribed off-label for previous medical indications, such as depression and obesity. Long-term exposure to high doses of amphetamines in some animal species is known to result in the development of abnormal dopamine systems or nerve damage, but in humans with ADHD, pharmaceutical amphetamines appear to promote brain development and neuronal growth. Magnetic resonance imaging research (MRI) reviews indicate that long-term treatment with amphetamines reduces abnormalities in brain structures and function found in subjects with ADHD, and improves function in some parts of the brain, such as the right caudate nucleus of the basal ganglia.
Research reviews of clinical stimulants have established the safety and effectiveness of long-term sustained use of amphetamines for the treatment of ADHD. Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD covering 2 years have demonstrated the effectiveness and safety of treatment. Two reviews have shown that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (ie, hyperactivity, poor attention, and impulsivity), improving quality of life and academic achievement, and resulting in improvements in a large number of functional outcomes in 9 outcome categories related to academics, antisocial behavior, driving, non-drug use, obesity, employment, self-esteem, use of services (ie, academic, occupational, health, financial, and legal services), and social functions. One review highlights nine months of randomized controlled trials of amphetamine treatment for ADHD in children who found an average increase in IQ points of 4.5, a continuous increase in attention, and a steady decline in disruptive and hyperactive behaviors. Other reviews indicate that, based on the longest follow-up study conducted to date, lifelong stimulation therapy initiated during childhood continues to be effective in controlling the symptoms of ADHD and reducing the risk of developing substance use disorders as adults.
Current ADHD models suggest that this is associated with functional impairment in some brain neurotransmitter systems; this functional impairment involves the interruption of dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the noradrenergic projection of the coeruleus locus to the prefrontal cortex. Psychostimulants such as methylphenidate and amphetamine are effective in treating ADHD because they increase the activity of neurotransmitters in this system. About 80% of those using this stimulant see improvement in ADHD symptoms. Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better at school, are less distracted and impulsive, and have longer attention spans. The Cochrane Collaboration review on ADHD treatment in children, adolescents, and adults with pharmaceutical amphetamines states that while these drugs improve short-term symptoms, they have higher rates of discontinuation than non-stimulant drugs because of adverse side effects. A Cochrane Collaboration review on the treatment of ADHD in children with tic disorders such as Tourette syndrome suggests that generalized stimulants do not make tics worse, but high doses of dextroamphetamine may exacerbate tics in some individuals.
Improved performance
Cognitive performance
In 2015, a systematic review and high quality meta-analysis of clinical trials found that, when used at low doses (therapeutic), amphetamines resulted in simple but unambiguous improvements in cognition, including working memory, long-term episodic memory, inhibitory control, and several aspects attention, in normal healthy adults; this cognitive enhancement effect of amphetamines is known to be partially mediated through the indirect activation of both dopamine receptors D 1 and adrenoceptors? 2 in the prefrontal cortex. A systematic review of 2014 found that low doses of amphetamines also increased memory consolidation, which in turn led to increased memory of information. Therapeutic doses of amphetamine also increase the efficiency of cortical tissue, an effect that mediates improvement in working memory in all individuals. Amphetamine and other ADHD stimulants also enhance the meaning of the task (motivation to perform the task) and increase the passion (wake), in turn promoting the behavior directed towards the goal. Stimulants such as amphetamines can improve performance on difficult and tedious tasks and are used by some students as a study and test aid. Based on a self-reported study of self-reported stimulants, 5-35% students use a transferable ADHD stimulant, primarily used for performance improvement rather than recreational drugs. However, high doses of amphetamines above the therapeutic range may interfere with memory work and other aspects of cognitive control.
Physical performance
Amphetamines are used by some athletes for the effect of improving psychological and athletic performance, such as increased endurance and alertness; however, the use of non-medical amphetamines is prohibited at sporting events organized by college, national, and international anti-doping agencies. In healthy people at oral therapeutic doses, amphetamine has been shown to increase muscle strength, acceleration, athletic performance under anaerobic conditions, and endurance (ie, delay onset of fatigue), while increasing reaction time. Amphetamine increases endurance and reaction time primarily through reuptake inhibition and smoothing of dopamine in the central nervous system. Amphetamines and other dopaminergic drugs also increase the power output at a steady level of perceived power by ignoring the "safety switch" which allows the increased core temperature limit to access the normally forbidden reserve capacity. In therapeutic doses, the adverse effects of amphetamine do not impede athletic performance; however, at much higher doses, amphetamines can cause devastating effects on performance, such as rapid muscle breakdown and increased body temperature.
Recreation
Dextroamphetamine is also used recreatively as an euphoriant and aphrodisiac, and like other amphetamines is used as a club drug because of its energetic and high euphoria. Dextroamphetamine is considered to have high potential for recreational abuse because individuals typically report feelings of euphoria, more alert, and more energetic after taking the drug. Dextroamphetamine large doses can cause dextroamphetamine overdose symptoms. The recreational user sometimes opens the dexedrine capsule and destroys its contents to grunt or then dissolve it in water and inject it. Injections into the bloodstream can be harmful because insoluble fillers inside the tablet may block the small blood vessels. Chronic excessive use of dextroamphetamine may cause severe drug dependence, leading to withdrawal symptoms when drug use ceases.
Maps Dextroamphetamine
Contraindications
According to the International Program on Chemical Security (IPCS) and the US Food and Drug Administration (USFDA), amphetamines are contraindicated in people with a history of drug abuse, cardiovascular disease, severe agitation, or severe anxiety. It is also contraindicated in people who currently have advanced arteriosclerosis (hardening of the arteries), glaucoma (increased eye pressure), hyperthyroidism (excessive production of thyroid hormones), or moderate to severe hypertension. These institutions show that people who have had an allergic reaction to other stimulants or who use monoamine oxidase inhibitors (MAOIs) should not take amphetamines, although the safe concurrent use of amphetamines and monoamine oxidase inhibitors has been documented. These bodies also state that anyone with anorexia nervosa, bipolar disorder, depression, hypertension, liver or kidney problems, mania, psychosis, Raynaud's phenomenon, seizures, thyroid problems, tics or Tourette syndrome should monitor their symptoms while taking amphetamines. Evidence from human studies suggests that the use of therapeutic amphetamines does not cause developmental abnormalities in fetuses or newborns (ie, these are not human teratogens), but amphetamine abuse poses a risk to the fetus. Amphetamine has also been shown to pass to breast milk, so IPCS and USFDA advise mothers to avoid breastfeeding when using it. Because of the potential for reversible growth disorders, the USFDA recommends high monitoring and weight loss of children and adolescents who are prescribed amphetamine pharmaceuticals.
Side effects
Physical
At normal therapeutic doses, the physical side effects of amphetamines vary greatly by age and from person to person. Cardiovascular side effects may include hypertension or hypotension of the vasovagal response, Raynaud's phenomenon (reduced blood flow to the hands and feet), and tachycardia (increased heart rate). Sexual side effects in men may include erectile dysfunction, frequent erections, or prolonged erections. Abdominal side effects may include abdominal pain, loss of appetite, nausea, and weight loss. Other potential side effects include blurred vision, dry mouth, excessive teeth grinding, nosebleeds, sweating, medicamentous rhinitis (drug-induced nasal congestion), reduced seizure threshold, and tics (a movement disorder). Hazardous physical side effects are rare in certain pharmaceutical doses.
Amphetamine stimulates the medullary respiratory center, producing faster and deeper breathing. In normal people with therapeutic doses, these effects are usually not seen, but when respiration is compromised, it may be proven. Amphetamine also induces contractions in the bladder sphincter, the muscle that controls the urine, which can cause difficulty urinating. This effect can be useful in treating bedwetting and loss of bladder control. The effects of amphetamines on the gastrointestinal tract are unpredictable. If intestinal activity, amphetamines can reduce gastrointestinal motility (the rate at which the content moves through the digestive system); However, amphetamines can increase motility when smooth muscle of the channel is relaxed. Amphetamine also has little analgesic effect and can increase the opioid pain-relieving effect.
USFDA-assigned studies from 2011 show that in children, young adults, and adults there is no association between serious serious cardiovascular events (sudden death, heart attack, and stroke) and medical use of amphetamines or other ADHD stimulants. However, amphetamine drugs are contraindicated in individuals with cardiovascular disease.
Psychological
In normal therapeutic doses, the most common psychological side effects of amphetamines include increased alertness, fear, concentration, initiative, self-confidence, and socialization, mood swings (joyful mood followed by a slightly depressed mood), insomnia or awake, and decreased fatigue. Less common side effects include anxiety, libido changes, grandiosity, irritability, repetitive or obsessive behavior, and anxiety; this effect depends on the user's personality and current mental state. Amphetamine psychosis (eg, delusions and paranoia) can occur in heavy users. Although very rare, this psychosis can also occur in therapeutic doses during long-term therapy. According to the USFDA, "there is no systematic evidence" that stimulants produce aggressive or hostile behavior.
Amphetamine has also been shown to result in conditioned place preference in humans using therapeutic doses, which means that individuals get a preference for spending time in places where they have previously used amphetamine.
Overdose
Overdose amphetamine can cause many different symptoms, but is rarely fatal with proper care. The severity of overdose symptoms increases with the dose and decreases with drug tolerance to amphetamines. Individuals who are tolerant have been known to consume as much as 5 grams of amphetamine in a day, which is about 100 times greater than daily therapeutic doses. The symptoms of moderate and very large overdoses are listed below; Fatal amphibamin poisoning usually also involves seizures and coma. In 2013, overdose in amphetamines, methamphetamines, and other compounds involved in "amphetamine use disorders" resulted in about 3,788 deaths worldwide ( 3,425-4,145 deaths, 95% confidence).
Pathological overactivation of the mesolimbic pathway, the dopamine pathway connecting the ventral ventral region to the nucleus accumbens, plays a central role in amphetamine addiction. Individuals who frequently overdose on amphetamines during recreational use have a high risk of developing amphetamine addiction, since recurrent overdose gradually increases the accumbal rate? FosB, a "molecular switch" and "master master protein" for addiction. After the nucleus accumbens? FosB is quite expressed, it begins to increase the severity of addictive behavior (ie, looking for compulsive drugs) with a further increase in its expression. While there is currently no effective cure for treating amphetamine addiction, regularly engaging in sustainable aerobic exercise seems to reduce the risk of developing such addiction. Regular aerobic exercise regularly also appears to be an effective treatment for amphetamine addiction; exercise therapy improves clinical treatment outcomes and can be used as a combination therapy with cognitive behavioral therapy, which is currently the best available clinical care.
Dependency
Addiction is a serious risk with the use of severe recreational amphetamines but may not arise from typical long-term medical use at therapeutic doses. Drug tolerance is growing rapidly in the misuse of amphetamine (ie, recreational amphetamine overdoses), so extended periods of use require larger doses of the drug to achieve the same effect.
Biomolecular mechanism
The use of chronic amphetamine in excessive doses leads to alteration of gene expression in the mesocorticolimbic projection, which appears through transcriptional and epigenetic mechanisms. The most important transcription factor that produces this change is? FosB, cAMP element binding protein (CREB), and nuclear factor kappa B (NF-? B). Fosb is the most important biomolecular mechanism in addiction because Fosb's overexpression in middle-spaced neurons of type D1 in the accumbens nucleus is necessary and sufficient for many nerve adaptations and behavioral effects (eg, increased expression dependent on self-administration and reward sensitization drugs) seen in drug addiction. Once? FosB is sufficiently expressed, it induces an addictive state that gets progressively worse with a further increase in the FosB expression. It has been implicated in alcoholism, cannabinoids, cocaine, methylphenidate, nicotine, opioids, phencyclidine, propofol, and amphetamine substitutions, among others.
? JunD, transcription factors, and G9a, the histone methyltransferase enzyme, both opposed to Fosb's function and inhibited the increase in expression. Simply over-expressed? JunD in nucleus accumbens with viral vectors can actually block many of the nerve changes and behaviors seen in chronic drug abuse (ie, changes mediated by? FosB). Fosb also plays an important role in regulating behavioral responses to natural rewards, such as good food, sex, and exercise. Because both natural rewards and addictive drugs induce expression? FosB (that is, they cause the brain to produce more), this chronic appreciation can result in the same pathological state of addiction. Consequently, Fosb is the most significant factor involved in amphetamine-induced and amphetamine-induced sex addiction, which is compulsive sexual behavior resulting from excessive sexual activity and amphetamine use. This sex addiction is associated with dopamine dysregulation syndrome that occurs in some patients taking dopaminergic drugs.
The effects of amphetamine on gene regulation are both dose-dependent and route-dependent. Most studies of gene regulation and addiction are based on animal studies with intravenous administration of amphetamines at very high doses. Several studies that have used the equivalent dose of human therapy (adjusted weight) and oral administration suggest that these changes, if they occur, are relatively small. This suggests that the medical use of amphetamines does not significantly affect gene regulation.
Pharmacological treatments
In 2015, there is no effective pharmacotherapy for amphetamine addiction. Reviews from 2015 and 2016 show that TAAR1 selective agonists have significant therapeutic potential as a treatment for psychostimulary addiction; however, in February 2016, the only compound known to function as a TAAR1 selective agonist was an experimental drug. Amphetamine addiction is largely mediated through increased activation of dopamine receptors and NMDA co-localization receptors NMDA in nucleus accumbens; magnesium ions inhibit NMDA receptors by blocking the calcium channel of the receptor. One review suggested that, based on animal testing, the use of pathological psychostimulants (which trigger addiction) significantly reduces the level of intracellular magnesium throughout the brain. Additional magnesium treatment has been shown to reduce amphetamine self-administration (ie, self-administered dose) in humans, but it is not an effective monotherapy for amphetamine addiction.
Treatment behavior
Current cognitive behavioral therapy is the most effective clinical treatment for psychostimulary addiction. In addition, research on the neurobiological effects of physical exercise shows that daily aerobic exercise, especially endurance exercises (eg, marathon run), prevents the development of drug addiction and is an effective additional therapy (ie, additional treatment) for amphetamine addiction. Exercise leads to better treatment outcomes when used as an adjunct treatment, especially for psychostimulant addiction. Specifically, aerobic exercise decreases the administration of psychostimulant self-administration, reduces recovery (ie, relapsing) of drug-seeking, and induces increased dopamine receptor D 2 (DRD2) density in the striatum. This is the opposite of the use of pathological stimulation, which induces decreased striatal DRD2 density. One review noted that exercise can also prevent the development of drug addiction by altering the immunoreactivity of FosB or c-Fos in the striatum or other parts of the reward system.
Dependence and tethering
According to other Cochrane Collaboration reviews about withdrawal in individuals who compulsively use amphetamine and methamphetamine, "when chronic heavy users suddenly discontinue amphetamine use, many reports of limited-time withdrawal syndrome occur within 24 hours of their last dose." This review notes that withdrawal symptoms in chronic high-dose users is common, occurs in about 88% of cases, and persists for 3-4 weeks with the "stuck" phase marked during the first week. Symptoms of withdrawal of amphetamines may include anxiety, drug cravings, depression, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or drowsiness, and lucid dreams. This review shows that the severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence. Symptoms of mild withdrawal from cessation of amphetamine treatment at therapeutic doses can be avoided by reducing the dose.
Toxicity
In rodents and primates, high doses of amphetamines cause dopaminergic neurotoxicity, or damage to dopamine neurons, characterized by terminal dopamine degeneration and reduced transporter and receptor function. There is no evidence that amphetamines are directly neurotoxic in humans. However, large doses of amphetamines indirectly can cause dopaminergic neurotoxicity as a result of hyperpyrexia, excessive reactive oxygen species formation, and increased dopamine autoxidation. Animal models of neurotoxicity from high doses of amphetamine exposure suggest that the occurrence of hyperpyrexia (ie, core body temperature> = Ã, 40Ã,  ° C) is required for the development of amphetamine-induced neurotoxicity. A rise in brain temperature over 40Ã, ° C probably promotes the development of amphetamine-induced neurotoxicity in laboratory animals by facilitating the production of reactive oxygen species, disrupting the function of cellular proteins, and temporarily increasing the permeability of blood brain barrier.
Psychosis
Severe amphetamine overdose can cause stimulatory psychosis that may involve multiple symptoms, such as delusions and paranoia. A Cochrane Collaboration review on treatment for amphetamines, dextroamphetamine, and methamphetamine psychosis states that about 5-15% users fail to recover completely. According to the same review, there is at least one trial that suggests an effective antipsychotic drug resolves the symptoms of acute amphetamine psychosis. Psychosis very rarely arises from therapeutic use.
Interactions
Many types of substances are known to interact with amphetamines, resulting in altered drug action or amphetamine metabolism, interacting substances, or both. An enzyme inhibitor that metabolizes amphetamines (eg, CYP2D6 and FMO3) will lengthen the elimination half-life, which means that the effect will last longer. Amphetamine also interacts with MAOIs, particularly monoamine oxidase A inhibitors, because MAOI and amphetamines increase plasma catecholamines (ie, norepinephrine and dopamine); Therefore, concurrent use is dangerous. Amphetamine modulates the activity of most psychoactive drugs. In particular, amphetamines can decrease the effects of sedatives and depressants and increase the effects of stimulants and antidepressants. Amphetamine may also decrease the antihypertensive and antipsychotic effects due to their effect on blood pressure and dopamine. Zinc supplements can reduce the minimum effective dose of amphetamine when used for the treatment of ADHD.
Pharmacology
Pharmacodynamics
Amphetamines and their enantiomers have been identified as potent agonists of an amine-related receptor 1 (TAAR1), a GPCR, discovered in 2001, which is important for the regulation of the monoaminergic system in the brain. TAAR1 activation increases cAMP production by activating adenylyl cyclase and inhibiting the function of dopamine transporters, norepinephrine transporters, and serotonin transporters, and promotes the release of monoamine neurotransmitters. The amphetamine enantiomers are also substrates for the transporters of nerve-specific synaptic vesicles called VMAT2. When amphetamines are taken by VMAT2, the vesicles release (effluxes) dopamine, norepinephrine, and serotonin, among other monoamines, to the cytosol instead.
Dextroamphetamine (dextrorotary enastomer) and levoamphetamine (enantiomer levorotary) have identical pharmacodynamics, but the affinity for binding of their biomolecular targets varies. Dextroamphetamine is a stronger agonist than TAAR1 compared to levoamphetamine. As a result, dextroamphetamine produces central nervous system (CNS) stimulation three to four times more than levoamphetamine; However, levoamphetamine has a slightly larger cardiovascular and peripheral effects.
Related endogenous compounds
Amphetamines have structures and functions that are very similar to endogenous trace amines, naturally occurring neurotransmitter molecules produced in the human body and brain. Among these groups, the most closely related compounds are phenethylamine, the parent compound of amphetamines, and N -methylphenethylamine , an isomer of amphetamine (ie, it has an identical molecular formula). In humans, phenethylamine is produced directly from L-phenylalanine by the amino acid decarboxylase enzyme (AADC), which converts L-DOPA to dopamine as well. In turn, N -methylphenethylamine is metabolized from phenethylamine by phenylethanolamine N-methyltransferase, the same enzyme that metabolizes norepinephrine to epinephrine. Like amphetamines, both phenethylamine and N -methylphenethylamine regulate monoamine neurotransmission through TAAR1 ; unlike amphetamines, both of these substances are broken down by monoamine oxidase B, and therefore have a shorter half-life than amphetamine.
Pharmacokinetics
Oral amphetamine oral bioavailability varies with gastrointestinal pH; it is well absorbed from the intestine, and bioavailability is usually over 75% for dextroamphetamine. Amphetamine is a weak base with p K a 9.9; consequently, when the pH is basic, more drugs are in the lipid-soluble base form, and are more absorbed through the lipid-rich cell membrane of the intestinal epithelium. In contrast, acidic pH means the drug is mainly in the form of cationic (salt) that is soluble in water, and less absorbed. About 15-40% of amphetamines circulating in the bloodstream are bound by plasma proteins. After absorption, amphetamines are readily distributed to most tissues in the body, with high concentrations occurring in cerebrospinal fluid and brain tissue.
The half-life of amphetamine enantiomers is different and varies with urinary pH. At normal urinary pH, half of dextroamphetamine and levoamphetamine life respectively 9-11 and clock 11-14 . Extremely acidic urine will reduce the half-life of the enantiomers up to 7 hours; Highly alkaline urine will increase the half-life to 34 hours. The release of direct and extended releases of salts from both isomers reach peak plasma concentrations at 3 hours and 7 hours post-dose respectively. Amphetamines are removed through the kidney, with <30% -40% of the excreted drug unchanged at normal urine pH. When the basic urine pH, amphetamine is in its free base form, so less is excreted. When the urine pH is abnormal, urinary recovery of amphetamines can range from a low of 1% to a high of 75%, depending on whether the urine is too basic or acidic, respectively. After oral administration, amphetamines appear in the urine within 3 hours. About 90% of the digestible amphetamines are removed 3 days after the last oral dose.
CYP2D6, dopamine? -hydroxylase (DBH), flavin-containing monooxygenase 3 (FMO3), butat-CoA ligase (XM-ligase), and glycine N-acyltransferase (GLYAT) are enzymes known to metabolize their amphetamines or metabolites in humans. Amphetamines have a variety of excreted metabolic products, including 4-hydroxyamphetamine, 4-hydroxynorephedrine, 4-hydroxyphenylacetone, benzoic acid, hypuratic acid and norephedrine. , and phenylacetone. Among these metabolites, active sympathomimetics are 4-hydroxyamphetamine , 4-hydroxynorephedrine , and norephedrine. The main metabolic pathway involves aromatic hydroxylation, aliphatic alpha and beta hydroxylation, N-oxidation, N-dealkylation, and deamination. Known metabolic pathways, detectable metabolites, and human metabolic enzymes include the following:
History, society and culture
Racemic amphetamine was first synthesized under the chemical name "phenylisopropylamine" in Berlin, 1887 by Romanian chemist Lazar Edeleanu. It was not widely marketed until 1932, when Smith's pharmaceutical company, Kline & amp; France (now known as GlaxoSmithKline) introduced it in the form of a Benzedrine inhaler to be used as a bronchodilator. In particular, the amphetamine contained in the Benzedrine inhaler is a free base liquid, not a chloride or sulphate salt.
Three years later, in 1935, the medical community became aware of the properties of amphetamine stimulants, especially dextroamphetamine, and in 1937 Smith, Kline, and french tablets were introduced under the Dexedrine tradename. In the United States, Dexedrine is approved to treat narcolepsy, attention disorders, and obesity. In Canada indications include epilepsy and parkinsonism. Dextroamphetamine is marketed in various other forms in subsequent decades, mainly by Smith, Kline, and French, as some combinations of drugs include a mixture of dextroamphetamine and amobarbital (barbiturates) sold under the trade name Dexamyl and, in the 1950s, an extension of release capsule ("Spansule"). Preparations containing dextroamphetamine were also used in World War II as a treatment against fatigue.
It quickly became clear that dextroamphetamine and other amphetamines had great potential for abuse, although they were not strictly controlled until 1970, when the Comprehensive Drug Abuse and Comprehensive Prevention Act was passed by the United States Congress. Dextroamphetamine, along with other sympathomimetics, is eventually classified as Schedule II, the most rigorous category possible for drugs with government-recognized medical use. Internationally, it is available under the names AmfeDyn (Italy), Curban (USA), Obetrol (Switzerland), Simpamina (Italy), Dexedrine/GSK (US & Canada), Dexedrine/UCB (UK), Dextropa (Portugal)), and Stild (Spain).
In October 2010, GlaxoSmithKline sold the rights to Dexedrine Spansule to Amedra Pharmaceuticals (a subsidiary of CorePharma).
The US Air Force uses dextroamphetamine as one of its "pill go", which is given to pilots in a long mission to help them stay focused and alert. In contrast, "no-go pills" are used after the mission is completed, to combat the effects of missions and "go-pill". Agricultural Incidents Tarnak is linked by media reports about the use of these drugs to long-term fatigue pilots. The military does not accept this explanation, citing the lack of similar incidents. New stimulant drugs or awareness-raising agents with different side effect profiles, such as modafinil, are under investigation and are sometimes excluded for this reason.
Formulation
Dextroamphetamine sulfate
In the United States, immediate release (IR) dextroamphetamine sulfate formulations are generally available as 5 mg and 10 mg tablets, marketed by Barr (Teva Pharmaceutical Industries), Mallinckrodt Pharmaceuticals, Wilshire Pharmaceuticals, Aurobindo Pharmaceutical USA and CorePharma. Previous IR tablets sold under the brand name Dexedrine and Dextrostat have been discontinued but by 2015 IR tablets become available under the Zenzedi brand name, offered as 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg and 30 mg tablets. Dextroamphetamine sulfate is also available as a preparation of a controlled release capsule (CR) with a strength of 5 mg, 10 mg, and 15 mg under the brand name Dexedrine Spansule, with a generic version marketed by Barr and Mallinckrodt. The bubblegum-scented oral solution is available under the brand name ProCentra, produced by FSC Pediatrics, designed to be an easier method of administration in children who have difficulty swallowing tablets, each 5 mL containing 5 mg dextroamphetamine. The conversion rate between dextroamphetamine sulfate to amphetamine free base is.728.
In Australia, dexamphetamine is available in 100 instant instant 5 mg tablets as a generic drug. or delayed preparation of dextroamphetamine release may be exacerbated by each chemist. Similarly, in the United Kingdom it is only available in 5 mg instant sulfate release tablet under the generic name dextroamphetamine sulphate which is available under the brand name Dexedrine before UCB Pharma divests the product to another pharmaceutical company (Auden Mckenzie).
Lisdexamfetamine
Dextroamphetamine is an active metabolite of prodrug lisdexamfetamine (L-lysine-dextroamphetamine), available under the brand name Vyvanse (lisdexamfetamine dimesylate). Dextroamphetamine is liberated from lisdexamfetamine enzymatically after contact with red blood cells. This conversion is limited by the enzyme, which prevents the concentration of dextroamphetamine in high blood and reduces the addiction and abuse of drug lisdexamfetamine in clinical doses. Vyvanse is marketed as a once-daily dose because it provides a slow release of dextroamphetamine into the body. Vyvanse is available as a capsule, and chewable tablets, and in seven strengths; 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg. The conversion rate between lisdexamfetamine dimesylate (Vyvanse) to the dextroamphetamine base was 29.5%.
Adderall
Other pharmaceuticals containing dextroamphetamine are commonly known by the brand name Adderall. It is available as a direct release (IR) tablet and extended release capsule (XR). Adderall contains the same amount of four amphetamine salts:
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- One quarter racemate (d, l-) amphetamine aspartate monohydrate
- One-quarter dextroamphetamine saccharate
- A quarter of dextroamphetamine sulfate
- One quarter racemate (d, l-) amphetamine sulfate
Adderall has a total amphetamine base equivalent of 63%. While the enantiomeric ratio with dextroamphetamine salts for levoamphetamine salts was 3: 1, the basic content of amphetamine was 75.9% dextroamphetamine, 24.1% levoamphetamine.
Note
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Reference notes
References
External links
- Dextroamphetamine consumer information from Drugs.com
- Poison Information Monograph (PIM 178: Dexamphetamine Sulphate)
Source of the article : Wikipedia
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