AMPHETAMINE SULFATE

First marketed in 1931

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 Search

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	H2O4S
Molecular Weight	98.078
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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	( + / - )

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208147s000lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Synaptic vesicular amine transporter 57 Target ID: CHEMBL1893 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7751968	Inhibitor 8297
Dopamine transporter 180 Target ID: CHEMBL238 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=15602501	Modulator 828

Conditions

Condition	Modality	Targets	Highest Phase	Product
Attention deficit hyperactivity disorder 68 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208147s000lbl.pdf	Primary		Approved 8429	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 2015

C_max

Value	Dose	Co-administered	Analyte	Population
120 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28936175/	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

Value	Dose	Co-administered	Analyte	Population
1727 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28936175/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28936175/	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

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 707 OCT1 512 OCT2 647 OCT3 150 P-gp 1461 BCRP 699	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://academic.oup.com/ijnp/article/13/7/905/668243?login=true	no
P-gp 1650	inhibitor 3277 Sources: https://academic.oup.com/ijnp/article/13/7/905/668243?login=true	no
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12746108/	yes [IC50 320 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 10.5 uM]
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 202 uM]
OCT3 150	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 460 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://dmd.aspetjournals.org/content/34/7/1116.short	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9264312/	yes

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B3-084875	http://www.3bsc.com/index/pro_info.php?id=126757
AHH Chemical co.,ltd	MT-50602	http://www.ahhchemical.com/product/MT-50602.html
Alfa Chemistry	300-62-9	https://www.alfa-chemistry.com/d-l-amphetamine-hydrochloride-cas-300-62-9-item-291370.htm
Aurora Fine Chemicals LLC	A01.300.744	http://online.aurorafinechemicals.com/info?ID=A01.300.744
Aurora Fine Chemicals LLC	K02.105.366	http://online.aurorafinechemicals.com/info?ID=K02.105.366
ChemMol	49416149	http://www.chemmol.com/chemmol/49416149.html
ChemMol	99068612	http://www.chemmol.com/chemmol/99068612.html
ChemMol	99117795	http://www.chemmol.com/chemmol/99117795.html
Clearsynth	CS-BX-00510	https://www.clearsynth.com/en/CSBX00510.html
Clearsynth	CS-O-10412	https://www.clearsynth.com/en/CSO10412.html
Debye Scientific	DB-047697	http://www.debyesci.com/cas_300-62-9.html
LGC Standards	LGCAMP0741.05-01	https://www.lgcstandards.com/US/en/p/LGCAMP0741.05-01
Sigma-Aldrich	A-007_CERILLIAN	https://www.sigmaaldrich.com/catalog/product/cerillian/a007?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	A-011_CERILLIAN	https://www.sigmaaldrich.com/catalog/product/cerillian/a011?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	610240_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/610240?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S007732	http://www.smolecule.com/products/s007732
Smolecule	S518779	http://www.smolecule.com/products/s518779
THE BioTek	bt-255830	https://www.thebiotek.com/product/inhibitors/bt-255830
THE BioTek	bt-259704	https://www.thebiotek.com/product/inhibitors/bt-259704
mcule	MCULE-4193952437	https://mcule.com/MCULE-4193952437/

PubMed

Title	Date	PubMed
Effect of chronic amphetamine exposure on stereotyped behavior: implications for pathogenesis of l-dopa-induced dyskinesias.	1975	1170714
The behavioral pharmacology of butaclamol hydrochloride (AY-23,028), a new potent neuroleptic drug.	1975 Apr 30	1171496
Acute subarachnoid hemorrhage.	1975 Jul 7	1173423
The anticataleptic effect of 7-OH-DPAT: are dopamine D3 receptors involved?	1999	10651103
Enantiomer-specific high-performance liquid chromatography with fluorescence detection of methamphetamines in abusers' hair and urine.	1999 Dec	10611609
Pharmacological properties of some xanthone derivatives.	1999 Jul-Aug	10635365
5-HT2 receptor antagonism reduces hyperactivity induced by amphetamine, cocaine, and MK-801 but not D1 agonist C-APB.	1999 Jun	10371652
Differential regional zif268 messenger RNA expression in an escalating dose/binge model of amphetamine-induced psychosis.	2000	10683413
Inhibition of amphetamine- and apomorphine-induced behavioural effects by neuropeptide Y Y(1) receptor antagonist BIBO 3304.	2000 Apr 27	10760371
Regulation of the human norepinephrine transporter by cocaine and amphetamine.	2000 Dec	11082428
[Fatal intracerebral hemorrhage after amphetamine intake].	2000 Jul 31	10962919
Amphetamine abuse during pregnancy: environmental factors and outcome after 14-15 years.	2000 Jun	10954143
Effect of dopamine agonists and antagonists on the lorazepam withdrawal syndrome in rats.	2000 Mar	10744342
Effects of repeated withdrawal from continuous amphetamine administration on brain reward function in rats.	2000 Nov	11140337
Delivery of a GDNF gene into the substantia nigra after a progressive 6-OHDA lesion maintains functional nigrostriatal connections.	2000 Nov	11031079
Amphetamine-induced toxicity in dopamine terminals in CD-1 and C57BL/6J mice: complex roles for oxygen-based species and temperature regulation.	2001	11731100
Behavioral sensitization in humans.	2001	11681593
Evaluation of the alpha2C-adrenoceptor as a neuropsychiatric drug target studies in transgenic mouse models.	2001 Apr 6	11358337
Attention-deficit/hyperactivity disorder in adults: beyond controversy.	2001 Aug	11483145
Stability of Adderall in extemporaneously compounded oral liquids.	2001 Aug 1	11494787
Developmental aspects of psychostimulant treatment in children and adolescents with attention-deficit/hyperactivity disorder.	2001 Dec	11765290
Role of hypothalamic neuropeptide Y (NPY) in the change of feeding behavior induced by repeated treatment of amphetamine.	2001 Dec 7	12005258
[Myocardial infarction caused by amphetamine].	2001 Feb	11321995
Transcranial magnetic stimulation in an amphetamine hyperactivity model of mania.	2001 Feb	11256461
Placebo-controlled evaluation of amphetamine mixture-dextroamphetamine salts and amphetamine salts (Adderall): efficacy rate and side effects.	2001 Jan	11134474
Effects of drugs of abuse on response accuracy and bias under a delayed matching-to-sample procedure in squirrel monkeys.	2001 Jul	11548110
Evaluation of nigrostriatal dopaminergic function in adult +/+ and +/- BDNF mutant mice.	2001 Jul	11421589
Acute myocardial infarction caused by amphetamines: a case report and review of the literature.	2001 Jun	11453588
Locomotor effects of acute and repeated threshold doses of amphetamine and methylphenidate: relative roles of dopamine and norepinephrine.	2001 Mar	11181919
Short-term cardiovascular effects of methylphenidate and adderall.	2001 May	11349696
Cholecystokinin2 receptor-deficient mice display altered function of brain dopaminergic system.	2001 Nov	11702094
Double-blind, placebo-controlled study of single-dose amphetamine formulations in ADHD.	2001 Nov	11699800
Changes in the performance of schedule-induced polydipsia (SIP) in rats after arecoline and amphetamine treatments.	2001 Oct	11699569
Pilot randomized controlled study of dexamphetamine substitution for amphetamine dependence.	2001 Sep	11672493
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	11418936
Serotonin1B receptor ligands in the nucleus accumbens shell do not affect the discriminative stimulus effects of amphetamine in rats.	2001 Sep-Oct	11990062
Retrospective comparison of Adderall and methylphenidate in the treatment of attention deficit hyperactivity disorder.	2001 Spring	11322743
D-amphetamine-induced behavioral sensitization: effect of lesioning dopaminergic terminals in the medial prefrontal cortex, the amygdala and the entorhinal cortex.	2002	11823062
The effects of delayed rewards, tokens, and stimulant medication on sportsmanlike behavior with ADHD-diagnosed children.	2002 Apr	11961910
A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder.	2002 Aug	12165576
Spontaneous novelty seeking and amphetamine-induced conditioning and sensitization in adult mice: evidence of dissociation as a function of age at weaning.	2002 Aug	12093596
Assessment of silver and gold substrates for the detection of amphetamine sulfate by surface enhanced Raman scattering (SERS).	2002 Feb	11913874
Effects of amphetamine on the plus-maze discriminative avoidance task in mice.	2002 Feb	11862369
24-hour ambulatory blood pressure monitoring in male children receiving stimulant therapy.	2002 Jul-Aug	12086544
Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a drug-placebo and drug-drug response curve analysis of a naturalistic study.	2002 Jun	12135536
CaMKII regulates amphetamine-induced ERK1/2 phosphorylation in striatal neurons.	2002 Jun 12	12060798
The effect of nitrostyrene on cell proliferation and macrophage immune responses.	2002 May	12066846
The neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one affects dopamine-mediated behavior in rodents.	2002 May	11981591
Spatial and temporal profile of haloperidol-induced immediate-early gene expression and phosphoCREB binding in the dorsal and ventral striatum of amphetamine-sensitized rats.	2002 Sep 15	12125044
Case series: Adderall augmentation of serotonin reuptake inhibitors in childhood-onset obsessive compulsive disorder.	2002 Summer	12188985

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Fri Dec 15 14:58:17 GMT 2023` Edited by `admin` on `Fri Dec 15 14:58:17 GMT 2023`
Record UNII	6DPV8NK46S
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMPHETAMINE SULFATE

Systematic Name

English

AMPHETAMINE SULFATE [ORANGE BOOK]

Common Name

English

AMFETAMINE SULFATE [EP MONOGRAPH]

Common Name

English

AMFETAMINE SULFATE

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