AMPHETAMINE PHOSPHATE

First marketed in 1931

Details

Stereochemistry	RACEMIC
Molecular Formula	C9H13N.H3O4P
Molecular Weight	233.2014
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OP(O)(O)=O.CC(N)CC1=CC=CC=C1

InChI

InChIKey=ZHVLGOLHHYJSBZ-UHFFFAOYSA-N

InChI=1S/C9H13N.H3O4P/c1-8(10)7-9-5-3-2-4-6-9;1-5(2,3)4/h2-6,8H,7,10H2,1H3;(H3,1,2,3,4)

HIDE SMILES / InChI

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
[Amphetamine-induced psychosis].	1998	11552236
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
SB-243213; a selective 5-HT2C receptor inverse agonist with improved anxiolytic profile: lack of tolerance and withdrawal anxiety.	2001 Aug	11489455
Attention-deficit/hyperactivity disorder in adults: beyond controversy.	2001 Aug	11483145
Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder.	2001 Aug	11483144
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
Effects of drugs of abuse on response accuracy and bias under a delayed matching-to-sample procedure in squirrel monkeys.	2001 Jul	11548110
Adderall and the FDA.	2001 Jul	11437005
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
Induction of tolerance to the suppressant effect of the neurotensin analogue NT69L on amphetamine-induced hyperactivity.	2001 Jun 22	11430916
Mutant mice lacking the cholecystokinin2 receptor show a dopamine-dependent hyperactivity and a behavioral sensitization to morphine.	2001 Jun 22	11403953
SLI381: a long-acting psychostimulant preparation for the treatment of attention-deficit hyperactivity disorder.	2001 Nov	11772303
Pharmacotherapies for attention-deficit/hyperactivity disorder: expected-cost analysis.	2001 Nov	11768842
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
Maturational increases in c-fos expression in the ascending dopamine systems.	2001 Sep 15	11494405
Serotonin1B receptor ligands in the nucleus accumbens shell do not affect the discriminative stimulus effects of amphetamine in rats.	2001 Sep-Oct	11990062
Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a reanalysis using drug-placebo and drug-drug response curve methodology.	2001 Summer	11436957
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
Adderall and seizures.	2002 Apr	11931590
Amphetamine salt compound treatment for adults with attention deficit hyperactivity disorder.	2002 Apr	11914167
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
Synthesis and D(2)-like binding affinity of new derivatives of N-(1-ethyl-2-pyrrolidinylmethyl)-4,5-dihydro-1H-benzo[g]indole-3-carboxamide and related 4H-[1]benzothiopyrano[4,3-b]pyrrole and 5,6-dihydro-4H-benzo[6,7]cyclohepta[b]pyrrole-3-carboxamide analogues.	2002 Aug	12057638
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
Cocaine and amphetamine depress striatal GABAergic synaptic transmission through D2 dopamine receptors.	2002 Feb	11790512
Dopamine transporter-dependent induction of C-Fos in HEK cells.	2002 Jul	12112414
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
Cocaine and amphetamine attenuate the discriminative stimulus effects of naltrexone in opioid-dependent rhesus monkeys.	2002 Jun	12023543
CaMKII regulates amphetamine-induced ERK1/2 phosphorylation in striatal neurons.	2002 Jun 12	12060798
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	11879792
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
Efficacy of Adderall for Attention-Deficit/Hyperactivity Disorder: a meta-analysis.	2002 Sep	12142863
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
Effect of amphetamine repeated treatment on the feeding behavior in neuropeptide Y-overexpressing mice.	2002 Sep 6	12183048
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)

Name

Type

Language

AMPHETAMINE PHOSPHATE

Systematic Name

English

AMFETAMINE PHOSPHATE [INCB GREEN LIST]

Common Name

English

.BETA.-AMINOPROPYLBENZENE PHOSPHATE

Systematic Name

English

(±)-DESOXYNOREPHEDRINE PHOSPHATE

Common Name

English

DL-AMPHETAMINE PHOSPHATE

Common Name

English

.BETA.-PHENYLISOPROPYLAMINE PHOSPHATE

Common Name

English

AMFETAMINE PHOSPHATE

Common Name

English

AKTEDRON

Brand Name

English

1-PHENYL-2-AMINOPROPANE PHOSPHATE

Systematic Name

English

.ALPHA.-METHYLBENZENEETHANAMINE PHOSPHATE

Systematic Name

English

AMPHETAMINE PHOSPHATE [MI]

Common Name

English

BENZENEETHANAMINE, .ALPHA.-METHYL-, PHOSPHATE (1:1)

Systematic Name

English

ACTEMIN

Brand Name

English

(±)-.ALPHA.-METHYLPHENETHYLAMINE PHOSPHATE

Systematic Name

English

BENZENEETHANAMINE, .ALPHA.-METHYL-, (±)-, PHOSPHATE (1:1)

Systematic Name

English

Code System Code Type Description

EVMPD

SUB36020