Details of the Drug

General Information of Drug (ID: DMMIHVP)

• Drug Name: Dextroamphetamine
• Synonyms: D-Amphetamine; dextroamphetamine; Dexamphetamine; Dexamfetamine; (S)-Amphetamine; Dexadrine; (+)-(S)-Amphetamine; Dexedrine; (2S)-1-phenylpropan-2-amine; (S)-(+)-Amphetamine; Dextrostat; Desamfetamina; (S)-1-Phenyl-2-propylamine; Dexidrine; Sympamin; Dephadren; Amsustain; (+)-Phenaminum; (+)-alpha-Methylphenethylamine; (S)-1-Phenyl-2-aminopropane; (+)-alpha-Methylphenylethylamine; D-(S)-Amphetamine; (S)-(+)-beta-Phenylisopropylamine; 51-64-9; (S)-alpha-Phenylethylamine; (2S)-(+)-Amphetamine; Benzedrine; Dexacaps; Dexamfetamina; Dexamfetaminum; Dexamphetaminum; Dexanfetamina; Isoamycin; Propisamine; Psychedrine; Raphetamine; Rhinalator; Simpatedrin; Sympamine; Sympatedrine; Weckamine; Desamfetamina [DCIT]; Dexedrine Spansule; Dextroamphetamine [USAN]; Dextroamphetamine resin complex; D-AM; Dexamfetamina [INN-Spanish]; Dexamfetamine (INN); Dexamfetaminum [INN-Latin]; Dexamphetaminum [INN-Latin]; Dexanfetamina [INN-Spanish]; Dexedrine (TN); Dextro-Amphetamine; Dextro-Amphetamine Sulfate; Dextroamphetamine (USAN); Dextrostat (TN); Dl-Amphetamine; Dl-Benzedrine; Fenylo-izopropylaminyl; Beta-phenyl-isopropylamine; D-alpha-methylphenethylamine; Alpha-Methylphenethylamine, d-form; S(+)-Amphetamine; D-(+)-Amphetamine; D-1-Phenyl-2-aminopropan; D-1-Phenyl-2-aminopropan [German]; D-1-Phenyl-2-aminopropane; D-2-Amino-1-phenylpropane; Dl-1-Phenyl-2-aminopropane; Benzeneethanamine, alpha-methyl-, (aS)-(9CI); Phenethylamine, alpha-methyl-, (+)-(8CI); (+/-)-Benzedrine; (+/-)-Desoxynorephedrine; (+/-)-beta-Phenylisopropylamine; (S)-1-Phenyl-2-propanamine; (S)-alpha-Methylphenethylamine; (S)-alpha-methylbenzeneethanamine; (alphaS)-alpha-methylbenzeneethanamine; dextroamphetamine sulfate (oral liquid, ADHD), Auriga

Indication

Disease Entry	ICD 11	Status	REF
Attention deficit hyperactivity disorder	6A05.Z	Approved	[1]
Depression	6A70-6A7Z	Approved	[2]
Narcolepsy	7A20	Approved	[1]

• Therapeutic Class: Central Nervous System Stimulants
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 135.21
  Logarithm of the Partition Coefficient (xlogp); 1.8
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 1
• ADMET Property:
  Bioavailability: 75% of drug becomes completely available to its intended biological destination(s) [3]
  Clearance: The clearance of drug is 17 L/h [4]
  Elimination: 40% of drug is excreted from urine in the unchanged form [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 11.75 hours [6]
  Metabolism: The drug is metabolized via the cytochrome P-450 2D6 in the liver to 4-hydroxyamphetamine and later conjugated by sulfotransferase or glucoronyltransferase [7]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 7.39587 micromolar/kg/day [8]
  Vd: The volume of distribution (Vd) of drug is 195 L [4]
  Water Solubility: The ability of drug to dissolve in water is measured as 1 mg/mL [5]
• Chemical Identifiers:
  Formula: C9H13N
  IUPAC Name: (2S)-1-phenylpropan-2-amine
  Canonical SMILES: C[C@@H](CC1=CC=CC=C1)N
  InChI: InChI=1S/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3/t8-/m0/s1
  InChIKey: KWTSXDURSIMDCE-QMMMGPOBSA-N
• Cross-matching ID:
  PubChem CID: 5826
  ChEBI ID: CHEBI:4469
  CAS Number: 51-64-9
  DrugBank ID: DB01576
  TTD ID: D0T3LF
  VARIDT ID: DR00675
  INTEDE ID: DR1759
  ACDINA ID: D00189
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Trace amine-associated receptor-1 (TAAR1)	TTIU98M	TAAR1_HUMAN	Modulator	[9]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[10]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[11]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[11]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Gene/Protein Processing	[11]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Gene/Protein Processing	[11]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Gene/Protein Processing	[11]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Gene/Protein Processing	[11]
BH3-interacting domain death agonist (BID)	OTOSHSHU	BID_HUMAN	Gene/Protein Processing	[11]
Brain-derived neurotrophic factor (BDNF)	OTLGH7EW	BDNF_HUMAN	Drug Response	[12]
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Drug Response	[13]
Disrupted in schizophrenia 1 protein (DISC1)	OT43AW4H	DISC1_HUMAN	Drug Response	[14]

Molecular Expression Atlas of This Drug

• The Studied Disease: Attention deficit hyperactivity disorder
• ICD Disease Classification: 6A05.Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Trace amine-associated receptor-1 (TAAR1)	DTT	TAAR1	6.12E-01	-0.01	-0.06
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	5.64E-01	2.36E-02	1.75E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Dextroamphetamine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Tromethamine	DMOBLGK	Moderate	as urine pH determines the ionization state of weakly acidic or weakly alkaline drugs. Dextroamphetamine caused by Tromethamine mediated altered urine pH.	Acidosis [5C73]	[15]
Methylene blue	DMJAPE7	Major	Additive hypertensive effects by the combination of Dextroamphetamine and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[16]
Droxidopa	DM5YF4M	Moderate	Additive hypertensive effects by the combination of Dextroamphetamine and Droxidopa.	Autonomic nervous system disorder [8D87]	[17]
Esketamine	DMVU687	Major	Additive hypertensive effects by the combination of Dextroamphetamine and Esketamine.	Depression [6A70-6A7Z]	[18]
SODIUM CITRATE	DMHPD2Y	Moderate	as urine pH determines the ionization state of weakly acidic or weakly alkaline drugs. Dextroamphetamine caused by SODIUM CITRATE mediated altered urine pH.	Discovery agent [N.A.]	[15]
Sodium acetate anhydrous	DMH21E0	Moderate	as urine pH determines the ionization state of weakly acidic or weakly alkaline drugs. Dextroamphetamine caused by Sodium acetate anhydrous mediated altered urine pH.	Hypo-osmolality/hyponatraemia [5C72]	[15]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Dextroamphetamine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[19]
Glycerol phenylbutyrate	DMDGRQO	Moderate	Decreased metabolism of Dextroamphetamine caused by Glycerol phenylbutyrate mediated inhibition of CYP450 enzyme.	Liver disease [DB90-DB9Z]	[20]
Ozanimod	DMT6AM2	Major	Additive hypertensive effects by the combination of Dextroamphetamine and Ozanimod.	Multiple sclerosis [8A40]	[16]
Safinamide	DM0YWJC	Major	Additive hypertensive effects by the combination of Dextroamphetamine and Safinamide.	Parkinsonism [8A00]	[16]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Allura red AC dye	E00338	33258	Colorant
Cetyl alcohol	E00061	2682	Coating agent; Emollient; Emulsifying agent; Stiffening agent
D&C red no. 27	E00381	83511	Colorant
D&C red no. 33	E00261	19116	Colorant
FD&C blue no. 1	E00263	19700	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Hydrazine yellow	E00409	164825	Colorant
Isopropyl alcohol	E00070	3776	Antimicrobial preservative; Solvent
Oleic acid	E00421	445639	Emulsifying agent; Penetration agent; Solubilizing agent
Quinoline yellow WS	E00309	24671	Colorant
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Stearic acid	E00079	5281	Emulsifying agent; Solubilizing agent; Viscosity-controlling agent; lubricant
Sunset yellow FCF	E00255	17730	Colorant
Ammonia	E00007	222	Alkalizing agent
Butyl alcohol	E00011	263	Flavoring agent; Solvent
Calcium sulfate anhydrous	E00303	24497	Desiccant; Diluent
Crospovidone	E00626	Not Available	Disintegrant
Dextrin	E00359	62698	Binding agent; Diluent; Microencapsulating agent; Stiffening agent; Suspending agent; Viscosity-controlling agent
Dibutyl sebacate	E00160	7986	Plasticizing agent
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Lithol rubin BCA	E00607	135423095	Colorant
Magnesium stearate	E00208	11177	lubricant
Medium-chain triglyceride	E00640	Not Available	Emollient; Lubricant; Surfactant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Potassium hydroxide	E00233	14797	Alkalizing agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Saccharose	E00091	5988	Binding agent; Coating agent; Cryoprotectant; Diluent; Flavoring agent; Suspending agent; Viscosity-controlling agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Vinylpyrrolidone	E00668	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Water	E00035	962	Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Dextroamphetamine 10 mg capsule	10 mg	Extended Release Oral Capsule	Oral
Dextroamphetamine 15 mg capsule	15 mg	Extended Release Oral Capsule	Oral
Dextroamphetamine 5 mg capsule	5 mg	Extended Release Oral Capsule	Oral
Dextroamphetamine 15 mg tablet	15 mg	Oral Tablet	Oral
Dextroamphetamine 20 mg tablet	20 mg	Oral Tablet	Oral
Dextroamphetamine 30 mg tablet	30 mg	Oral Tablet	Oral
Dextroamphetamine 7.5 mg tablet	7.5 mg	Oral Tablet	Oral
Dextroamphetamine 10 mg tablet	10 mg	Oral Tablet	Oral
Dextroamphetamine 2.5 mg tablet	2.5 mg	Oral Tablet	Oral
Dextroamphetamine 5 mg tablet	5 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Dextroamphetamine FDA Label
• [3] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [4] Dolder PC, Strajhar P, Vizeli P, Hammann F, Odermatt A, Liechti ME: Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects. Front Pharmacol. 2017 Sep 7;8:617. doi: 10.3389/fphar.2017.00617. eCollection 2017.
• [5] BDDCS applied to over 900 drugs
• [6] Pharmacokinetics of dexamphetamine in acute stroke. Clin Neuropharmacol. 2003 Sep-Oct;26(5):270-6.
• [7] Clinical pharmacokinetics of amfetamine and related substances: monitoring in conventional and non-conventional matrices. Clin Pharmacokinet. 2004;43(3):157-85. doi: 10.2165/00003088-200443030-00002.
• [8] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [9] Methamphetamine and HIV-1-induced neurotoxicity: role of trace amine associated receptor 1 cAMP signaling in astrocytes. Neuropharmacology. 2014 Oct;85:499-507.
• [10] Involvement of CYP2D6 in the in vitro metabolism of amphetamine, two N-alkylamphetamines and their 4-methoxylated derivatives. Xenobiotica. 1999 Jul;29(7):719-32.
• [11] An insight into the hepatocellular death induced by amphetamines, individually and in combination: the involvement of necrosis and apoptosis. Arch Toxicol. 2013 Dec;87(12):2165-85. doi: 10.1007/s00204-013-1082-9. Epub 2013 Jul 3.
• [12] An association study of the brain-derived neurotrophic factor Val66Met polymorphism and amphetamine response. Am J Med Genet B Neuropsychiatr Genet. 2006 Sep 5;141B(6):576-83. doi: 10.1002/ajmg.b.30327.
• [13] Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6186-91. doi: 10.1073/pnas.0931309100. Epub 2003 Apr 25.
• [14] Misassembly of full-length Disrupted-in-Schizophrenia 1 protein is linked to altered dopamine homeostasis and behavioral deficits. Mol Psychiatry. 2016 Nov;21(11):1561-1572. doi: 10.1038/mp.2015.194. Epub 2016 Jan 12.
• [15] Anggard E, Jonsson LE, Hogmark AL, Gunne LM "Amphetamine metabolism in amphetamine psychosis." Clin Pharmacol Ther 14 (1973): 870-80. [PMID: 4729903]
• [16] Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
• [17] Product Information. Northera (droxidopa). Chelsea Therapeutics Inc, Charlotte, NC.
• [18] Cerner Multum, Inc. "Australian Product Information.".
• [19] Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
• [20] Cerner Multum, Inc. "UK Summary of Product Characteristics.".