U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula 2C9H13N.H2O4S
Molecular Weight 368.491
Optical Activity ( + / - )
Defined Stereocenters 0 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMPHETAMINE SULFATE

SMILES

OS(O)(=O)=O.CC(N)CC1=CC=CC=C1.CC(N)CC2=CC=CC=C2

InChI

InChIKey=PYHRZPFZZDCOPH-UHFFFAOYSA-N
InChI=1S/2C9H13N.H2O4S/c2*1-8(10)7-9-5-3-2-4-6-9;1-5(2,3)4/h2*2-6,8H,7,10H2,1H3;(H2,1,2,3,4)

HIDE SMILES / InChI

Molecular Formula C9H13N
Molecular Weight 135.2062
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula H2O4S
Molecular Weight 98.078
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.caremark.com/portal/asset/FEP_Rationale_Amphetamine.pdf https://www.ncbi.nlm.nih.gov/pubmed/23539642 http://www.cesar.umd.edu/cesar/drugs/amphetamines.asp

Amphetamine is a potent central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. Amphetamine was discovered in 1887 and exists as two enantiomers: levoamphetamine and dextroamphetamine. The mode of therapeutic action in ADHD is not known. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. 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. Several currently prescribed amphetamine formulations contain both enantiomers, including Adderall, Dyanavel XR, and Evekeo, the last of which is racemic amphetamine sulfate. Amphetamine is also prescribed in enantiopure and prodrug form as dextroamphetamine and lisdexamfetamine respectively. Lisdexamfetamine is structurally different from amphetamine, and is inactive until it metabolizes into dextroamphetamine.

CNS Activity

Curator's Comment: Amphetamines readily cross the blood-brain barrier to reach their primary sites of action in the brain. The acute administration of amphetamine produces a wide range of dose-dependent behavioral changes, including increased arousal or wakefulness, anorexia, hyperactivity, perseverative movements, and, in particular, a state of pleasurable affect, elation, and euphoria, which can lead to the abuse of the drug.

Originator

Curator's Comment: Although a Japanese scientist called Mr. A Ogata, was the first to synthesize methamphetamine in 1919, it wasn’t until 1930 that it was realized that amphetamines raised the blood pressure. https://blackpoppymag.wordpress.com/substances/dexedrine-dexamphetamine/

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DYANAVEL XR

Approved Use

INDICATIONS Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and Narcolepsy. Attention Deficit Hyperactivity Disorder (ADHD) A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV®) implies the presence of hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least six of the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; “on the go;” excessive talking; blurting answers; can't wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met. Special Diagnostic Considerations: Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but of special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the child and not solely on the presence of the required number of DSM-IV® characteristics. Need for Comprehensive Treatment Program: Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all children with this syndrome. Stimulants are not intended for use in the child who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician's assessment of the chronicity and severity of the child's symptoms. Long-Term Use: The effectiveness of Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets for long-term use has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Dextroamphetamine Saccharate, Amphetamine Aspartate, Dextroamphetamine Sulfate and Amphetamine Sulfate Tablets for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

Launch Date

1.44521285E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
120 ng/mL
40.3 mg single, oral
dose: 40.3 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMPHETAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1727 ng × h/mL
40.3 mg single, oral
dose: 40.3 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMPHETAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.9 h
40.3 mg single, oral
dose: 40.3 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMPHETAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​Drug as victim

Drug as victim

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
The behavioral pharmacology of butaclamol hydrochloride (AY-23,028), a new potent neuroleptic drug.
1975 Apr 30
Acute subarachnoid hemorrhage.
1975 Jul 7
[Intracerebral hemorrhage following amphetamine use].
1998 Nov-Dec
The anticataleptic effect of 7-OH-DPAT: are dopamine D3 receptors involved?
1999
Atrioventricular nodal re-entrant tachycardia associated with stimulant treatment.
1999
The potentiating effect of sertraline and fluoxetine on amphetamine-induced locomotor activity is not mediated by serotonin.
1999 Apr
RGS mRNA expression in rat striatum: modulation by dopamine receptors and effects of repeated amphetamine administration.
1999 Apr
Comparison of dopamine receptor antagonists on hyperlocomotion induced by cocaine, amphetamine, MK-801 and the dopamine D1 agonist C-APB in mice.
1999 Aug
5-HT2 receptor antagonism reduces hyperactivity induced by amphetamine, cocaine, and MK-801 but not D1 agonist C-APB.
1999 Jun
Event-related potential indices of auditory selective attention in dependent amphetamine users.
1999 Jun 1
Effects of continuous exposure to light on behavioral dopaminergic supersensitivity.
1999 Jun 15
Acute pulmonary edema following amphetamine ingestion.
1999 Mar
Differential regulation of calmodulin content and calmodulin messenger RNA levels by acute and repeated, intermittent amphetamine in dopaminergic terminal and midbrain areas.
2000
Combined amphetamine and cocaine abuse caused mesencephalic ischemia in a 16-year-old boy - due to vasospasm?
2000
Differential regional zif268 messenger RNA expression in an escalating dose/binge model of amphetamine-induced psychosis.
2000
Selective lesions of the entorhinal cortex, the hippocampus, or the fimbria-fornix in rats: a comparison of effects on spontaneous and amphetamine-induced locomotion.
2000 Apr
Activation of neostriatal dopaminergic system in rats prevents toxic effects of picrotoxin administered into globus pallidus.
2000 Aug
Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers.
2000 Aug
Regulation of the human norepinephrine transporter by cocaine and amphetamine.
2000 Dec
[Fatal intracerebral hemorrhage after amphetamine intake].
2000 Jul 31
Effect of dopamine agonists and antagonists on the lorazepam withdrawal syndrome in rats.
2000 Mar
An evaluation of l-ephedrine neurotoxicity with respect to hyperthermia and caudate/putamen microdialysate levels of ephedrine, dopamine, serotonin, and glutamate.
2000 May
Effects of repeated withdrawal from continuous amphetamine administration on brain reward function in rats.
2000 Nov
Delivery of a GDNF gene into the substantia nigra after a progressive 6-OHDA lesion maintains functional nigrostriatal connections.
2000 Nov
Amphetamine-induced toxicity in dopamine terminals in CD-1 and C57BL/6J mice: complex roles for oxygen-based species and temperature regulation.
2001
Evaluation of the alpha2C-adrenoceptor as a neuropsychiatric drug target studies in transgenic mouse models.
2001 Apr 6
Attention-deficit/hyperactivity disorder in adults: beyond controversy.
2001 Aug
Stability of Adderall in extemporaneously compounded oral liquids.
2001 Aug 1
Developmental aspects of psychostimulant treatment in children and adolescents with attention-deficit/hyperactivity disorder.
2001 Dec
Role of hypothalamic neuropeptide Y (NPY) in the change of feeding behavior induced by repeated treatment of amphetamine.
2001 Dec 7
Transcranial magnetic stimulation in an amphetamine hyperactivity model of mania.
2001 Feb
Placebo-controlled evaluation of amphetamine mixture-dextroamphetamine salts and amphetamine salts (Adderall): efficacy rate and side effects.
2001 Jan
Behavioural and anti-psychotic effects of Ca2+ channel blockers in rhesus monkey.
2001 Jan 26
Adderall and the FDA.
2001 Jul
Evaluation of nigrostriatal dopaminergic function in adult +/+ and +/- BDNF mutant mice.
2001 Jul
Acute myocardial infarction caused by amphetamines: a case report and review of the literature.
2001 Jun
Amphetamine selectively blocks inhibitory glutamate transmission in dopamine neurons.
2001 Mar
Lobeline inhibits the neurochemical and behavioral effects of amphetamine.
2001 Mar
Pharmacotherapies for attention-deficit/hyperactivity disorder: expected-cost analysis.
2001 Nov
Changes in the performance of schedule-induced polydipsia (SIP) in rats after arecoline and amphetamine treatments.
2001 Oct
Pilot randomized controlled study of dexamphetamine substitution for amphetamine dependence.
2001 Sep
Differentially altered mGluR1 and mGluR5 mRNA expression in rat caudate nucleus and nucleus accumbens in the development and expression of behavioral sensitization to repeated amphetamine administration.
2001 Sep 1
Serotonin1B receptor ligands in the nucleus accumbens shell do not affect the discriminative stimulus effects of amphetamine in rats.
2001 Sep-Oct
D-amphetamine-induced behavioral sensitization: effect of lesioning dopaminergic terminals in the medial prefrontal cortex, the amygdala and the entorhinal cortex.
2002
A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder.
2002 Aug
Cocaine and amphetamine depress striatal GABAergic synaptic transmission through D2 dopamine receptors.
2002 Feb
24-hour ambulatory blood pressure monitoring in male children receiving stimulant therapy.
2002 Jul-Aug
CaMKII regulates amphetamine-induced ERK1/2 phosphorylation in striatal neurons.
2002 Jun 12
The ability of amphetamine to evoke arc (Arg 3.1) mRNA expression in the caudate, nucleus accumbens and neocortex is modulated by environmental context.
2002 Mar 15
The neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one affects dopamine-mediated behavior in rodents.
2002 May
Patents

Sample Use Guides

DYANAVEL XR (R (amphetamine) extended-release oral suspension) should be orally administered once daily in the morning with or without food. The dose should be individualized according to the needs and responses of the patient. Before administering the dose, shake the bottle of DYANAVEL XR. In children 6 years of age and older, start with 2.5 mg or 5 mg once daily in the morning. The dose may be increase
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: Amph increases the effects induced by βPEA on the LGC-55, indicating that Amph potentiates the effects generated by the biogenic amine βPEA
β-Phenylethylamine (βPEA) activates the amine-gated chloride channel LGC-55 more efficiently than amphetamine (Amph) (Km = 9 and 152 μm, respectively)
Substance Class Chemical
Created
by admin
on Wed Jul 05 22:30:22 UTC 2023
Edited
by admin
on Wed Jul 05 22:30:22 UTC 2023
Record UNII
6DPV8NK46S
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMPHETAMINE SULFATE
MI   ORANGE BOOK   USP   VANDF  
Systematic Name English
AMPHETAMINE SULFATE [ORANGE BOOK]
Common Name English
AMFETAMINE SULFATE [EP MONOGRAPH]
Common Name English
AMFETAMINE SULFATE
EP   INCB:GREEN LIST   MART.   WHO-DD  
Common Name English
BENZENEETHANAMINE, .ALPHA.-METHYL-, SULPHATE (2:1), (±)-
Common Name English
(±)-.ALPHA.-METHYLPHENETHYLAMINE SULFATE (2:1)
Systematic Name English
AMFETAMINE SULFATE [MART.]
Common Name English
AMPHETAMINE SULPHATE
Systematic Name English
DL-AMPHETAMINE SULFATE
Common Name English
EVEKEO ODT
Brand Name English
ASTEDIN
Common Name English
AMFETAMINE SULPHATE
Common Name English
.BETA.-PHENYLISOPYROPYLAMINESULFATE
Common Name English
(±)-2-AMINO-1-PHENYLPROPANE SULPHATE
Systematic Name English
AMPHETAMINE SULFATE [VANDF]
Common Name English
(±)-2-AMINO-1-PHENYLPROPANE SULFATE
Systematic Name English
(±)-.ALPHA.-METHYLPHENETHYLAMINE SULPHATE (2:1)
Systematic Name English
AMPHETAMINE SULFATE [MI]
Common Name English
AMFETAMINE SULFATE [EP IMPURITY]
Common Name English
AMPHETAMINE SULFATE [USP MONOGRAPH]
Common Name English
AMFETAMINE SULFATE [INCB:GREEN LIST]
Common Name English
Amfetamine sulfate [WHO-DD]
Common Name English
DL-AMPHETAMINE SULPHATE
Common Name English
NSC-170999
Code English
BENZENEETHANAMINE, .ALPHA.-METHYL-, SULFATE (2:1), (±)-
Common Name English
DELCOBESE COMPONENT AMPHETAMINE SULFATE
Common Name English
AMPHETAMINE SULFATE COMPONENT OF DELCOBESE
Common Name English
BENZEDRINE
Brand Name English
Classification Tree Code System Code
EPA PESTICIDE CODE 600085
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
NCI_THESAURUS C47795
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
DEA NO. 1100
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
Code System Code Type Description
CHEBI
2679
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
SMS_ID
100000085149
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
NCI_THESAURUS
C28822
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
ECHA (EC/EINECS)
200-457-8
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
DAILYMED
6DPV8NK46S
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
CHEBI
51063
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
EVMPD
SUB00438MIG
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
ChEMBL
CHEMBL405
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
RXCUI
81952
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY RxNorm
FDA UNII
6DPV8NK46S
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
DRUG BANK
DBSALT001205
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
CAS
60-13-9
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
EPA CompTox
DTXSID4020082
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
INCB IDS CODE
PA 003
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
MERCK INDEX
M1849
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY Merck Index
PUBCHEM
6055
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
PRIMARY
CAS
156-31-0
Created by admin on Wed Jul 05 22:30:22 UTC 2023 , Edited by admin on Wed Jul 05 22:30:22 UTC 2023
SUPERSEDED
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY