Amphetamine salts combo

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mixture of amphetamine products
Combination of
dextroamphetamine sulfate  ? Class
dextroamphetamine saccharate  ? Class
amphetamine sulfate  ? Class
amphetamine aspartate  ? Class
Clinical data
Trade names Adderall
Adderall ER
Adderall XR
AHFS/Drugs.com monograph
MedlinePlus a601234
Licence data US Daily Med:link
Pregnancy cat. C (US)
Legal status Schedule I (CA) Schedule II (US)
Dependence liability High
Routes (Medical) Oral, (Recreational) Oral, Insufflated, Intravenous
Identifiers
CAS number 51-64-9 YesY 300-62-9
ATC code N06BA02 N06BA01
PubChem CID 5826
DrugBank DB01576
ChemSpider 13852819 YesY
KEGG D03740 YesY
ChEBI CHEBI:2679 YesY
ChEMBL CHEMBL405 YesY
 N (what is this?)  (verify)

An amphetamine salts combo, also known as amphetamine salts, is a pharmaceutical drug consisting of mixed salts and enantiomers of amphetamine. Adderall, a medication commonly used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy, is an amphetamine salts combo, as are its generics.

Contents

History [edit]

In the Unites States, between 1965 and 1983 an "amphetamine salts combo" product was was offered in 10mg and 20mg strength through Obetrol Pharmaceuticals division of an American pharmaceutical company Rexar under the name Obetrol. Its indication was for exogenous obesity.

The formulation for the 1965-1983 Obetrol 10mg strength:

  • Methamphetamine saccharate 2.5mg
  • Methamphetamine hydrochloride 2.5mg
  • Amphetamine sulfate 2.5mg
  • 2.5mg dextroamphetamine sulfate 2.5mg[1]


It is used primarily for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. [2] It is a psychostimulant.

Adderall is a mixture of amphetamine salts consisting of equal amounts by mass of: [3]

It is a dopamine releasing agent, a norepinephrine releasing agent, and can be mildly serotonergic.[4]

It is available in two formulations: IR (Instant Release) and XR (Extended Release). The immediate release formulation is indicated for use in ADHD and narcolepsy,[5] while the XR formulation is approved for use only with ADHD.[4]

Some research suggests that long-term use of Adderall in children may stunt growth, and it has been associated with rare acute psychotic episodes.[6] When abused at high doses, the risk of experiencing side effects and the severity of side effects increases.

Adderall directly affects the mesolimbic reward pathway. Amphetamine salt preparations are considered to have high abuse potential, and are Schedule II controlled substances in the United States. The Safe Streets and Communities Act reclassified Adderall from Schedule III to Schedule I in Canada.[7]

Medical uses [edit]

Adderall is indicated for the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It has been used to treat obesity, but the American Society of Health-System Pharmacists does not recommend this use.[2]

Attention deficit hyperactivity disorder [edit]

Adderall has been shown to significantly reduce symptoms associated with ADHD and reportedly presents minimal side-effects. Depending on dosage, and ignoring potential side effects from on-going use or addiction, the beneficial effects of stimulant medications can last several hours, allowing improved performance throughout the day.[8] Compared to the similar medication methylphenidate (sold under the brand name Ritalin and others), studies have suggested that Adderall is slightly more potent and has a longer period of efficacy, especially at lower doses.[9] Adderall's efficacy results from Adderall's ability to inhibit reuptake of dopamine and the ability to increase dopamine levels.[citation needed] For those who experience adverse side effects to Ritalin or for whom Ritalin has become ineffective, Adderall is often recommended as a substitute.[10][11] A typical adult dosing is between 30–40 mg for Adderall XR.[12]

Dosing and administration [edit]

Adderall is marketed as either an immediate-release tablet Adderall, or an extended-release capsule Adderall XR.[5]

Adderall XR utilizes the Microtrol extended-release delivery system, incorporating two types of beads. The first dissolves immediately, releasing half of the medication, while the second type dissolves slowly, releasing the remaining medication four hours later. Maximum plasma concentration is achieved in seven hours, compared to instant-release Adderall, which reaches maximum plasma concentration within three hours. As a result of its high bioavailability, Adderall XR's effectiveness is not altered by food absorption in the gastrointestinal tract. However, mean plasma concentration is prolonged by 2.5 hours (using a 900-calorie standard high-fat meal as the control). Medications that alter urinary pH will cause variations in the amount and method of excretion, and usage should be monitored when taken concurrently with Adderall.[13]

Manufacturer's claims of instant release have been disputed. A US patent granted for Adderall[14] was a pharmaceutical composition patent listing a rapid immediate-release oral dosage form. No claim of increased or smooth drug delivery was made. A recent double-blind, placebo-controlled crossover study conducted among 35 children ages 5–12 indicated that patients behaved similarly to those having taken other immediate-release amphetamines. The authors found that sustained-release dexamphetamine (the main isomeric-amphetamine component of Adderall) had a longer duration of action, however D-amphetamine was less effective in the first few hours.[15]

Adverse effects [edit]

See also: Amphetamine effects and dextroamphetamine effects

Some Adderall side effects include dizziness, nervousness, headache and weight loss, as well as faster heartbeat combined with lower blood pressure. Hair loss (alopecia), decreased libido or sex drive, and bloody stools have also been reported. In addition, taking too much Adderall medicine initially could make attention-deficit hyperactivity disorder symptoms worse. Studies of long-term use of Adderall and methylphenidate in children have shown a temporary decrease in growth rate that does not affect final adult height.[16] Stimulant medications also decrease appetite in some people, leading to weight loss, and this effect is more common with mixed amphetamine salts than methylphenidate[16] or atomoxetine. Changes in vision have been reported with both Adderall and methylphenidate.[4][17] Women who are pregnant should avoid taking Adderall, especially during early pregnancy. Studies on rats show long-term neurological and behavioral changes resulting from prenatal and early postnatal exposure to amphetamines.[4][18] Warnings from the Patient Medication Guide for Adderall include serious cardiovascular events, sudden deaths, stroke, emergence of new psychotic or manic symptoms, aggression and blurred vision.[19][20]

Contraindications, interactions, and precautions [edit]

The following provides only general guidelines and is not comprehensive. Please refer to a more comprehensive list for further information regarding co-administration of amphetamine with other substances.

  • MAOIs (monoamine oxidase inhibitors, e.g., phenelzine, selegiline, iproniazid, etc.) —There is a high risk of a hypertensive crisis if amphetamine is administered within two weeks after last use of an MAOI type drug. Preliminary trials of low-dose amphetamine and MAOIs being administered together are in progress. However, this is to be done only under strict supervision of the prescribing parties.
  • SSRIs (selective serotonin reuptake inhibitors, e.g., fluvoxamine, citalopram, paroxetine, etc.) — While a common combination, and although rare, the risk for serotonin syndrome exists. (Use only when directed)
  • NRIs (norepinephrine reuptake inhibitors, e.g., atomoxetine, etc.) — NRI medications and amphetamine both enhance noradrenergic activity. Possible augmentation/potentiation of effects. (Use only when directed)
  • SNRIs (selective serotonin-norepinephrine reuptake inhibitors) — See SSRIs and NRIs.
  • Bupropion  — Both bupropion and amphetamine have noradrenergic and dopaminergic activity. Possible augmentation/potentiation of effects. Bupropion has pro-convulsant properties that may be enhanced or cumulatively potentiated by amphetamine.[21] (Use only when directed)
  • Tricyclics and related compounds (tricyclic antidepressant)  — See SNRIs and SSRIs. Possible potentiation of serotonin-, dopamine-, and norepinephrine-related drug effects. The combination of tricyclic and amphetamine compounds/other direct-acting sympathomimetics has been associated with increased sympathetic action. Adjustments to dose may be required. Concurrent use not generally recommended due to interaction between direct-acting sympathomimetics such as amphetamine and tricyclics. Indirect-acting sympathomimetics may have decreased efficacy when combined with tricyclics (tricyclic blockade may inhibit the action of some indirect-acting sympathomimetics).
  • CYP2D6 (liver enzyme) inhibitors, e.g., most SSRIs such as fluoxetine, citalopram, paroxetine, etc. Some anti-psychotics such as thioridazine, haloperidol, and levomepromazine, as well as cocaine, the opioid agonist methadone, and others. It is important to determine if any medication or drug taken is a CYP2D6 inhibitor. Taking a CYP2D6-inhibiting drug along with amphetamine will lead to an elevated level of amphetamine in the system, resulting in the drug's remaining in the body for a longer period, which can lead to undesirable and possibly serious side effects.

Pregnancy [edit]

Adderall is in FDA pregnancy category C.[22] This means that research conducted in animals has suggested that Adderall harms fetuses, but in certain cases the drug's use by pregnant women may be warranted.[23] It is not definitely known whether Adderall harms a developing human embryo or fetus. However, some research suggests that premature birth, low birth weight, or withdrawal symptoms may occur in a newborn if its mother took Adderall during pregnancy.[24]

Government warnings [edit]

On February 9, 2005, Health Canada suspended all sales of Adderall XR after data collected by manufacturer Shire Pharmaceuticals linked the drug to 12 sudden deaths in American children.[25] Further research found data suggesting use of Adderall resulted in an increased risk of cardiac defect and it is known that amphetamine class drugs like Adderall present a marked increase in heart rate and blood pressure.[26] Although more than 37 million prescriptions for Adderall were filled during the four years prior, the U.S. Food and Drug Administration could find no increased risk of sudden death among Adderall users.[25][27] In August 2005, Health Canada followed the committee report of three independent physicians and lifted the ban on Adderall XR.[28][29] Given that persons with ADHD are more likely to engage in risky or dangerous behavior, it has been suggested that stimulant medications for persons with ADHD may actually result in lower incidence of premature death.[30] The use of Adderall is generally not advised in those persons with pre-existing cardiac or mental illnesses. It is also not advised in persons who have a history of drug abuse.[5] Although FDA safety advisors voted 8 to 7 to issue a black box warning, the FDA's pediatric advisory committee refused to give the drug its most severe black box warning in March 2006.[31] A Black Box Warning regarding amphetamine abuse potential is in place, however. In September 2000, Britain's National Institute for Health and Clinical Excellence urged physicians not to prescribe Adderall or similar drugs to children under 5, and to exhaustively consider other approaches to behavioral modification before prescribing such drugs to children 5 and up.[32]

Prolonged use [edit]

Prolonged high doses of amphetamines followed by an abrupt cessation can result in extreme fatigue, insomnia, irritability, weight gain, mental depression, urination problems (sometimes mistaken for a urinary tract infection), and bloody stools. Chronic abuse of amphetamines can result in the manifestation of amphetamine psychosis;[4] occasionally this psychosis can occur at therapeutic doses during chronic therapy as a treatment emergent side effect.[6]

Chemistry [edit]

Adderall's effects are similar to other central nervous system (CNS) stimulants of the same class and preparation. (See amphetamine for details.)

Urinary and stomach pH levels can have a strong effect on DL-amphetamine excretion and absorption.[33] An acidic stomach and GI pH will decrease the absorption of Adderall,[13] and acidic urine levels will decrease the reabsorption of the drug through the renal system.[34] Co-administration of acidic substances (e.g., citric acid) causes decreased renal reabsorption of DL-amphetamine; whereas, alkaline agents (e.g., antacids) may cause a marked increase in renal tubular reabsorption. The increased reabsorption can increase the retention of amphetamines, with potential to result in dangerously high serum levels.[34]

Adderall XR [edit]

Adderall (mixed amphetamine salts) 20 mg XR

Adderall XR is the extended release version of the drug. The breakdown rate of Adderall XR is affected by many factors including urinary and stomach pH,[13][33] weight, sex, other medications being taken, and age. Alkalinity increases bioavailability, while acidity causes the drug to be excreted more quickly. Manufacturers claim that the mixture of salts in Adderall XR makes its effects more consistent and sustained.[35]

Metabolism [edit]

"The mean elimination half-life for d-amphetamine is 10 hours in adults; 11 hours in adolescents aged 13–17 years and weighing less than or equal to 75 kg/165 lbs; and 9 hours in children aged 6 to 12 years. For the l-amphetamine, the mean elimination half-life in adults is 13 hours; 13 to 14 hours in adolescents; and 11 hours in children aged 6 to 12 years. On a mg/kg body weight basis children have a higher clearance than adolescents or adults."[36](p2)

Generic forms [edit]

Adderall (mixed amphetamine salts) 30 mg IR

Both Adderall IR and Adderall XR are available as generic drugs,[37] and Adderall XR is also available as an authorized generic.[38][39][40] Authorized generics are manufactured by the brand name manufacturer but marketed and sold by a different company. The contents of authorized generics and the brand name drug are identical.

Mechanism of action [edit]

The molecular structure of amphetamine
Main article: Dextroamphetamine mechanism of action

Amphetamines are believed to exert their effects by binding to the monoamine transporters and increasing extracellular levels of the biogenic amines dopamine, norepinephrine, and serotonin.[citation needed] It is hypothesized that D-amphetamine acts primarily on the dopaminergic (DA) systems, while L-amphetamine is comparatively norepinephrinergic (NE)[citation needed]. The primary reinforcing and behavioral-stimulant effects of amphetamine, however, are linked to enhanced dopaminergic activity, primarily in the mesolimbic dopaminergic pathway. Amphetamine binds to the dopamine transporter (DAT) and blocks the transporter's ability to clear DA from the synaptic space. In addition, amphetamine is transported into the cell, which leads to dopamine efflux (DA is transported out of the cell and into the synaptic space via reverse transport of the DAT).

Amphetamine also possesses the ability to inhibit the enzymes monoamine oxidase-A and -B (MAO-A and MAO-B) in high doses[citation needed]. Amphetamine's ability to cause the inhibition of MAO results in the accumulation of monoamines: Amphetamine directly stimulates the release of these neurochemicals, resulting in a potent elevation in monoamine neurotransmission. The effect of amphetamines is to increase neurotransmitter availability in the synapse, by both releasing more neurotransmitters and prolonging their availability in the synapse by slowing their removal.

MAO-A is responsible for the breakdown of serotonin, dopamine, norepinephrine, and epinephrine. MAO-B is responsible for breaking down dopamine (more potently than MAO-A) and phenylethylamine (PEA), which has actions similar to those of amphetamine itself, and is thought to be involved in feelings of lust, confidence, obsession, and sexuality. Some of the first antidepressants successfully marketed are, in fact, monoamine oxidase inhibitors. However, MAO inhibition seen with amphetamine is not substantial enough in duration and quantity to entail the need for a tyramine-limited diet, unlike the more potent and long-lived MAO-inhibiting antidepressants.

With respect to central stimulant actions, the S(+) isomer (i.e., dextroamphetamine) is several times more potent than its R(-)enantiomer (i.e., levoamphetamine); this is not necessarily the case with other actions produced by amphetamine, in particular those produced in the periphery such as cardiovascular actions.[41] Dextroamphetamine induces more euphoria, whereas levoamphetamine induces more depression. The overall greater potency of the dextro form to central actions suggests that this form may have a higher potential for abuse.[42]

Adderall’s inclusion of levoamphetamine provides the pharmaceutical with a quicker onset and longer clinical effect compared to pharmaceuticals formulated exclusively of dextroamphetamine.[43] Although it seems the human brain has a preference for dextroamphetamine over levoamphetamine, it has been reported that certain children have a better clinical response to levoamphetamine.[44]

Performance-enhancing use [edit]

 This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (November 2012)

In addition to treatment of juveniles with ADHD, Adderall is sometimes prescribed for children who are not doing well in school but who don't have ADHD. But the tunnel-like focus the medicines provide has led growing numbers of teenagers and young adults to fake symptoms to obtain steady prescriptions for highly addictive medications that carry serious psychological dangers.[45]

In higher education [edit]

Adderall is widely used as a "study drug" at universities.[46] It enables the user to focus and stay awake. Stories of students writing papers continuously for an unusually long time or "cramming" all night for an exam with no loss of energy or concentration are common.[46]

Young adults are by far the fastest-growing segment of people taking ADHD medications. Nearly 14 million monthly prescriptions for the condition were written for Americans ages 20 to 39 in 2011, two and a half times the 5.6 million just four years before, according to the data company I.M.S. Health.[47] According to a 2010 U.S. National College Health Assessment, 8 percent of surveyed University students said they had used stimulants within the past 12 months that were not prescribed to them. Numbers from the Substance Abuse and Mental Health Services Administration found that 6.4 percent of full-time college students abused Adderall in 2007. But some studies have found that as many as 25 percent of students abused prescription stimulants.[48]

Adderall is in high demand on US campuses, often selling for very high prices. It is a Schedule II drug, and its sale is therefore a Class B felony. Possession without a prescription is also illegal.[49] It is often difficult to catch illegal Adderall sales because the pills are “easily concealed, odorless, and can be perceived as prescribed drugs.”

Survey results published in 2006 found that amphetamine salts like Adderall were used three times more on college campuses than methylphenidate (commonly known as Ritalin). White and Hispanic students used amphetamine salts far more often than black and Asian students.[50]

In sport [edit]

Many athletic organizations have restricted the usage of Adderall by athletes. The NCAA has banned the use of Adderall for its collegiate athletes without a prescription and adequate records of evaluation and diagnosis of ADHD.[51] Nevada State Athletic Commission has also banned athletes in the state from using Adderall. Tim Credeur was removed from a UFC fight on the finale of The Ultimate Fighter 7 because of a positive drug test due to his use of it. In the National Football League, New Orleans Saints kicker Garrett Hartley served a four-game suspension when the 2009 NFL regular season began because he tested positive for the banned stimulant. Cleveland Browns cornerback Joe Haden was suspended 4 games for using Adderall in 2012. The Arizona Cardinals tight end Ben Patrick received a four-game suspension as a result of using Adderall.[52]

The New York Giants running back Andre Brown faced a four-game suspension for violating NFL's performance-enhancing substance ban. Brown said: “It was something that I've been on since I've been in the league, which was Adderall. I just forgot to fill out some paperwork and that was it.” [53] Brown eventually won an appeal, and had his suspension lifted.[54] Another Giants player, Tyler Sash, was suspended for four games by the NFL in July 2012 after testing positive for Adderall four months earlier. The safety said in a statement that he took the drug legally and "under a doctor's care for an anxiety condition" to help him with public speaking.[55]

The New York Giants safety Will Hill was charged a four-game suspension for violating NFL's performance-enhancing substance ban. Hill said: “I received a doctor's prescription for Adderall prior to signing with the Giants.” [56]

New England Patriots cornerback Aqib Talib has been suspended four games by the NFL for violating the league's policy on performance enhancing substances. Talib released a statement saying his suspension was a result of testing positive for Adderall: "Around the beginning of training camp, I made a mistake by taking an Adderall pill without a prescription,".[57]

Philadelphia Phillies catcher Carlos Ruiz has been suspended 25 games by Major League Baseball for testing positive for the drug, effective at the start of the 2013 season. In a statement, Ruiz said, "I am sincerely regretful for my mistake in taking a prohibited stimulant." [58]

Recreational use [edit]

Adderall, as an amphetamine product, is used recreationally for its euphoric and stimulant properties.[59] These effects are often obtained when it is crushed, snorted or when dissolved in water and injected. Injecting it into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels.[60] When combined with alcohol, adverse symptoms of Adderall become apparent where the user forms short term psychosis and has no awareness of it, resulting in sudden rage or outburst. Prescription amphetamine is often obtained by those with a prescription and diverted and sold to those who do not have a prescription.[61] As a Schedule II drug, Adderall is considered to have a high potential for misuse and a high liability for dependence.[62][63] Amphetamine has the potential to cause withdrawal (mainly psychological) symptoms when ceasing use.[64]

Detection of use [edit]

Amphetamine is frequently measured in hair, oral fluid, sweat, or urine as part of a drug abuse testing program. Techniques such as immunoassay may cross-react with a number of sympathomimetics drugs, so chromatographic methods specific for amphetamine should be employed to prevent false-positive results. Chiral techniques may be employed to help distinguish the source of the drug, whether obtained legally (by prescription) or illegally or possibly as a result of formation from a prodrug such as lisdexamfetamine or selegiline. Chiral separation can be used to differentiate Adderall use from use of another prescription form of amphetamine or from use of illicit amphetamine, since Adderall is unique in having a 3:1 mixture of the d- and l-isomers.[65][66][67]

History [edit]

Adderall is available as an instant-release (IR) and an extended-release (XR) drug. Adderall instant-release is manufactured today by Teva and Barr Pharmaceuticals. Shire Pharmaceuticals, the creator of Adderall IR, no longer produces it. However, Shire does continue to manufacture the extended-release version of Adderall ("Adderall XR"). Richwood Pharmaceuticals (later merged with Shire) introduced the Adderall brand in 1996 in the form of a multi-dose, instant-release tablet derived from an original formula of the weight management drug Obetrol. In 2006, Shire agreed to sell rights to the Adderall name for this instant-release medication to Duramed Pharmaceuticals[68] DuraMed Pharmaceuticals was acquired by Teva Pharmaceuticals in 2008 when Teva completed its acquisition of Barr Pharmaceuticals (including Barr's Duramed division).[69] Therefore, following its acquisition of Duramed, Teva is in the somewhat unusual position of manufacturing both a generic formulation of Adderall instant-release (under its Barr Division) as well as "brand name" Adderall (under its DuraMed division.)

Reflecting the change in manufacturers from Shire Pharmaceuticals to Teva's DuraMed Pharmaceuticals, the "imprint" on Adderall instant-release tablets has changed. One side of the instant-release tablets now bears the barr Pharmaceuticals imprint, a lowercase letter "b" . This is a change from the previous uppercase "AD" imprint on the tablets.

The active ingredients of Adderall include a combination of dextroamphetamine and racemic DL-amphetamine salts with most common formulations being 75% dextro:25% levo amphetamine mixtures.[70] In 2001, Shire introduced an extended-release preparation of these ingredients in a variety of dosages under the brand name "Adderall XR," on which Shire retains exclusive patent rights until the patent expires, expected in 2018.[71] However, due to issues with Shire's inability to evergreen (extend the patent life by obtaining either a new FDA indication or application of other patent life) the patent for Adderall XR, the drug has become available in a generic form.[72] In 2009, Barr and Shire reached a settlement agreement permitting Barr to offer a generic form of the drug beginning April 1, 2009.[73]

Legal status [edit]

  • Canada: In March 2012, Canada passed the "Safe Streets and Communities Act" into law, which (in part) rescheduled amphetamines from Schedule III to Schedule I.
  • New Zealand: Stimulants are not prescribed in New Zealand. International travelers with valid prescriptions must declare them, the drugs will be taken, and the patient must go to a dispensary daily to receive their medications.
  • Japan: The use, production, and import of any medicine containing Methamphetamine or Amphetamine is prohibited.[74]
  • South Korea: Dextroamphetamine is a prohibited substance in South Korea, and amphetamine-based medications are therefore not prescribed. However, other stimulant medications such as Ritalin, Metadate CD, Concerta, and Strattera are prescribed.[75]
  • Thailand: Amphetamine and dextroamphetamine are classified as Type 1 Narcotics.[76]
  • United Nations: The United Nations Office on Drugs and Crime has recommended that Adderall should be administered only to those with a valid prescription and valid diagnosis. The UN believes that stimulant abuse is a problem and is trying to find a way to decrease the amount of people who abuse stimulants.[77]
  • United States: The United States Drug Enforcement Administration classifies Adderall as a Schedule II substance. According to the US DEA, these are substances with a high potential for abuse, but with legitimate and accepted medical uses. This makes it a criminal offense to possess Adderall without a valid prescription and limits the amount a medical provider can prescribe to a 90 day supply, which can be split into multiple separate prescriptions, the combination totaling 90 days supply and with instructions to the pharmacy for when the prescription may be filled.[78][79][80]

2011-12 shortage in U.S. market [edit]

In 2011 and 2012, there was a shortage of Adderall and Ritalin, particularly generic formulations, in U.S. pharmacies.[81] The shortage was caused by the Drug Enforcement Administration's annual limits on the manufacture of controlled substances. The Food and Drug Administration, which maintains a shortage list, stated that the DEA's Adderall quotas were too strict.[82] The DEA disagreed, arguing that drug manufacturers had caused the shortage by applying their quotas toward more lucrative kinds of amphetamine-based medications. The FDA listed amphetamine salts as a "resolved" drug shortage on November 29, 2012.[83]

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Phenethylamines
Amphetamines
Phenylisopropylamines
Phentermines
Cathinones
Phenylisobutylamines
Phenylalkylpyrrolidines
Catecholamines
(and close relatives)
Miscellaneous
Psychostimulants, agents used for ADHD, and nootropics (N06B)
Centrally acting sympathomimetics
Xanthine derivatives
Glutamate receptor
Eugeroics / Benzhydryl compounds
Histamine H3 receptor antagonists
GABAA α5 inverse agonists
Dopamine D1 receptor agonists
α7 nicotinic agonists / PAMs
Prolyl endopeptidase inhibitors
Alpha-adrenergic agonists
Plants
Antioxidants
Other psychostimulants and nootropics

M: PSO/PSI

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)
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