Lisdexamfetamine

Lisdexamfetamine


Systematic (IUPAC) name
(2S)-2,6-diamino-N-[(1S)-1-methyl-2-phenylethyl] hexanamide
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a607047
Pregnancy cat.	C
Legal status	Schedule II (US)
Routes	Oral
Pharmacokinetic data
Bioavailability	28%
Metabolism	Gastro-intestinal (initial); Hepatic (extensively CYP2D6) after conversion to d-amphetamine
Half-life	< 1 hour (prodrug molecule), 12-13 hours (d-amphetamine)
Excretion	Renal: ~2%
Identifiers
CAS number	608137-32-2^Y
ATC code	N06BA12
PubChem	CID 11597698
DrugBank	DB01255
ChemSpider	9772458^Y
UNII	H645GUL8KJ^Y
ChEMBL	CHEMBL1201222^N
Synonyms	(S)-2,6-diamino-N-[(S)-1-phenylpropan-2-yl]hexanamide
Chemical data
Formula	C₁₅H₂₅N₃O
Mol. mass	263.378 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C15H25N3O/c1-12(11-13-7-3-2-4-8-13)18-15(19)14(17)9-5-6-10-16/h2-4,7-8,12,14H,5-6,9-11,16-17H2,1H3,(H,18,19)/t12-,14-/m0/s1^Y Key:VOBHXZCDAVEXEY-JSGCOSHPSA-N^Y
N(what is this?) (verify)

Lisdexamphetamine (L-lysine-D-amphetamine; sold as Vyvanse) is a psychostimulant prodrug of the phenethylamine and amphetamine chemical classes. Its molecular structure consists of dextroamphetamine coupled with the essential amino acid L-lysine.

Lisdexamfetamine itself is inactive and acts as a prodrug to dextroamphetamine upon cleavage of the lysine portion of the molecule. It was developed for the intention of creating a longer-lasting and more difficult to abuse version of dextroamphetamine, as the requirement of conversion into dextroamphetamine via enzymes in the red blood cells increases its duration, regardless of the route of ingestion.^[1] There is no increased onset or effect as occurs with IV administration of dextroamphetamine compared to oral use of the same. Intravenously administered lisdexamfetamine produced likability effects similar to placebo, therefore affirming the drug's ability to reduce abuse potential.^[2]

Lisdexamfetamine is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in children six to twelve years and in adults as an integral part of a total treatment program that may include other measures (i.e., psychological, educational, social). The safety and efficacy of lisdexamfetamine dimesylate in patients three to five years old have not been established.^[3]

As opposed to Adderall, which contains roughly 75% dextroamphetamine and 25% levoamphetamine, lisdexamfetamine is a single-enantiomer (dextro) amphetamine formula. This pure formulation may reduce side effects, but certain individuals exhibit a better clinical response to the mixed isomer preparation.^[4]

Vyvanse is also being investigated for possible treatment of Major Depressive Disorder, cognitive impairment associated with Schizophrenia, Excessive Daytime Sleepiness, and Binge Eating Disorder.^[5]

1 Dosage
2 History
3 Misuse potential
- 3.1 Common side effects
- 3.2 Severe side effects
4 See also
5 References

Dosage

Lisdexamfetamine is available under the brand-name Vyvanse. Vyvanse comes in several different dosages (see table below). These dosages are usually labeled to be taken once daily.^[6]

Vyvanse dosage strengths available^[6]
Strength	Appearance	Imprint (unique label)
20 milligrams	Capsule with ivory colored body and cap	NRP104 or S489 20 mg
30 milligrams	Capsule with white colored body and orange colored cap	NRP104 or S489 30 mg
40 milligrams	Capsule with white colored body and teal colored cap	NRP104 or S489 40 mg
50 milligrams	Capsule with white colored body and blue colored cap	NRP104 or S489 50 mg
60 milligrams	Capsule with aqua blue colored body and cap	NRP104 or S489 60 mg
70 milligrams	Capsule with blue colored body and orange colored cap	NRP104 or S489 70 mg

25 mg of Vyvanse is molecularly equivalent to a 10 mg Dexedrine Spansule (both are about 7.425 mg dextroamphetamine base), although a 25 mg Vyvanse capsule is not commercially available.^[7] However, the molecular equivalence ratio does not mean that the respective doses of Vyvanse and Adderall XR (Spansule) are bioequivalent because the two formulations have slightly different pharmacokinetic profiles. For example, while the area under the curve for the aforementioned pharmaceuticals is equivalent, the peak exposure (C_max) to the active compound dextroamphetamine is about 50% higher for Vyvanse than for Dexedrine XR.^[7] The conversion rate of lisdexamfetamine to dextroamphetamine base is 0.2948^[8], meaning that each milligram of lisdexamphetamine is equivalent to 0.2948 mg of dextroamphetamine base.

History

Vyvanse was developed by New River Pharmaceuticals, who were bought by Shire Pharmaceuticals shortly before lisdexamfetamine began being marketed. Vyvanse is approved by the U.S. Food and Drug Administration (FDA) for the treatment of attention-deficit hyperactivity disorder.

On April 23, 2008, Vyvanse received FDA approval for the adult population ^[9]. In a randomized, double-blind, four-week phase III trial in adult patients with ADHD, 30, 50 or 70mg/day of oral lisdexamfetamine caused a significantly greater improvement in ADHD-Rating Scale total score than placebo.^[10]

On February 19, 2009, Health Canada approved 30 mg and 50 mg capsules of lisdexamphetamine for treatment of ADHD.^[11]

Misuse potential

Lisdexamfetamine has less potential for misuse than its active metabolite (dextroamphetamine) due to being initially inactive upon consumption via all methods and taking longer to metabolise than dextro-amphetamine (both results of being a pro-drug). Misuse of lisdexamfetamine may cause the same extent of cardiovascular side-effects as dextro-amphetamine, but again this risk is likely to be reduced due to the method of administration.

Common side effects

Common side effects (side effects that have average rates of presentation; usually presenting in >5% of patients) of lisdexamfetamine use include: ^[6]^[12]

Discomfort
Erectile Dysfunction
Dizziness
Mild agitation (restlessness)
Nausea
Xerostomia (dry mouth)
Bruxism (jaw clenching/grinding)
Anxiety
Diarrhea
Emesis (vomiting)
Headache
Insomnia (inability to sleep)
Weight loss (decreased appetite)
Euphoria
Diaphoresis (increased sweating)
Irritability
Parageusia (unpleasant taste)
Upper abdominal pain
Cold Feet or Hands
Rapid Heartbeat

Severe side effects

Very infrequent but possibly severe side effects requiring immediate medical attention may be caused by lisdexamfetamine; these serious reactions include:^[6]^[12]

Severe aggression - some patients have reported sudden mood changes, inability to control rage, physical abuse of others
Abnormal muscle weakness or tiredness
Anaphylaxis - a severe allergic reaction with effects including a rash, hives, itching, difficulty breathing, and generalized swelling.
Changes in vision
Dyspnea (shortness of breath)
Fever
Severe headache
Syncope (fainting)

Angina pectoris (severe chest pain)
Blurred vision
Cardiac dysrhythmias - a group of cardiovascular conditions in which the electrical activity of the heart is abnormal with effects ranging from a fast heartbeat to cardiac arrest and sudden death.
Seizures
Tics - sudden, stereotyped, nonrhythmic and repetitive motor movements and/or vocalizations.

Hallucinations
Muscle tremors
Severe irritability
Severe psychomotor agitation
Altered sexual ability or desire such as hypersexuality, male impotence, premature ejaculation, etc.
Tachycardia (fast heartbeat)
Slowed thinking
Unstable emotions

References

^ Lisdexamfetamine Dimesylate: A Prodrug Stimulant for the Treatment of ADHD in Children and Adults
^ Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusers.
^ "Lisdexamfetamine dimesylate (generic)." Brown University Psychopharmacology Update 19.7 (2008): 1-2. Academic Search Premier. EBSCO. Web. 12 Sept. 2010.
^ "Vyvanse Vs. Adderall
^ http://www.shire.com/shireplc/en/rd/pipeline
^ ^a ^b ^c ^d Vyvanse (Lisdexamfetamine Dimesylate) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList
^ ^a ^b FDA Approval of Vyvanse – Pharmacological Reviews
^ Moore, Elaine.The Amphetamine Debate: The Use of Adderall, Ritalin and Related Drugs for Behavior Modification, Neuroenhancement and Anti-Aging Purposes. McFarland, 2010, p. 91.
^ FDA Adult Approval of Vyvanse - FDA Label and Approval History
^ Weber J, Siddiqui, MA. [1].CNSDrugs 2009; 23(5): 419-425.doi: 10.2165/00023210-200923050-00005.
^ Health Canada Notice of Compliance - Vyvanse. February 19, 2009, retrieved on March 9, 2009.
^ ^a ^b Lisdexamfetamine Capsules Facts and Comparisons at Drugs.com

Stimulants (N06B)

Adamantanes	Adaphenoxate • Adapromine • Amantadine • Bromantane • Chlodantane • Gludantane • Memantine • Midantane

Adenosine antagonists	8-Chlorotheophylline • 8-Cyclopentyltheophylline • 8-Phenyltheophylline • Aminophylline • Caffeine • CGS-15943 • Dimethazan • Paraxanthine • SCH-58261 • Theobromine • Theophylline

Alkylamines	Cyclopentamine • Cypenamine • Cyprodenate • Heptaminol • Isometheptene • Methylhexaneamine • Octodrine • Propylhexedrine • Tuaminoheptane

Arylcyclohexylamines	Benocyclidine • Dieticyclidine • Esketamine • Eticyclidine • Gacyclidine • Ketamine • Phencyclamine • Phencyclidine • Rolicyclidine • Tenocyclidine • Tiletamine

Benzazepines	6-Br-APB • SKF-77434 • SKF-81297 • SKF-82958

Cholinergics	A-84543 • A-366,833 • ABT-202 • ABT-418 • AR-R17779 • Altinicline • Anabasine • Arecoline • Cotinine • Cytisine • Dianicline • Epibatidine • Epiboxidine • GTS-21 • Ispronicline • Nicotine • PHA-543,613 • PNU-120,596 • PNU-282,987 • Pozanicline • Rivanicline • Sazetidine A • SIB-1553A • SSR-180,711 • TC-1698 • TC-1827 • TC-2216 • TC-5619 • Tebanicline • UB-165 • Varenicline • WAY-317,538

Convulsants	Anatoxin-a • Bicuculline • DMCM • Flurothyl • Gabazine • Pentetrazol • Picrotoxin • Strychnine • Thujone

Eugeroics	Adrafinil • Armodafinil • CRL-40941 • Modafinil

Oxazolines	4-Methylaminorex • Aminorex • Clominorex • Cyclazodone • Fenozolone • Fluminorex • Pemoline • Thozalinone

Phenethylamines	1-(4-Methylphenyl)-2-aminobutane • 1-Phenyl-2-(piperidin-1-yl)pentan-3-one • 1-Methylamino-1-(3,4-methylenedioxyphenyl)propane • 2-Fluoroamphetamine • 2-Fluoromethamphetamine • 2-OH-PEA • 2-Phenyl-3-aminobutane • 2-Phenyl-3-methylaminobutane • 2,3-MDA • 3-Fluoroamphetamine • 3-Fluoroethamphetamine • 3-Fluoromethcathinone • 3-Methoxyamphetamine • 3-Methylamphetamine • 3,4-DMMC • 4-BMC • 4-Ethylamphetamine • 4-FA • 4-FMA • 4-MA • 4-MMA • 4-MTA • 6-FNE • Alfetamine • α-Ethylphenethylamine • Amfecloral • Amfepentorex • Amfepramone • Amidephrine • Amphetamine (Dextroamphetamine, Levoamphetamine) • Amphetaminil • Arbutamine • β-Methylphenethylamine • β-Phenylmethamphetamine • Benfluorex • Benzedrone • Benzphetamine • BDB (J) • BOH (Hydroxy-J) • BPAP • Buphedrone • Bupropion (Amfebutamone) • Butylone • Cathine • Cathinone • Chlorphentermine • Cinnamedrine • Clenbuterol • Clobenzorex • Cloforex • Clortermine • D-Deprenyl • Denopamine • Dimethoxyamphetamine • Dimethylamphetamine • Dimethylcathinone (Dimethylpropion, Metamfepramone) • Dobutamine • DOPA (Dextrodopa, Levodopa) • Dopamine • Dopexamine • Droxidopa • EBDB (Ethyl-J) • Ephedrine • Epinephrine (Adrenaline) • Epinine (Deoxyepinephrine) • Etafedrine • Ethcathinone (Ethylpropion) • Ethylamphetamine (Etilamfetamine) • Ethylnorepinephrine (Butanefrine) • Ethylone • Etilefrine • Famprofazone • Fenbutrazate • Fencamine • Fenethylline • Fenfluramine (Dexfenfluramine) • Fenmetramide • Fenproporex • Flephedrone • Fludorex • Furfenorex • Gepefrine • HMMA • Hordenine • Ibopamine • IMP • Indanylamphetamine • Isoetarine • Isoethcathinone • Isoprenaline (Isoproterenol) • L-Deprenyl (Selegiline) • Lefetamine • Lisdexamfetamine • Lophophine (Homomyristicylamine) • Manifaxine • MBDB (Methyl-J; "Eden") • MDA (Tenamfetamine) • MDBU • MDEA ("Eve") • MDMA ("Ecstasy", "Adam") • MDMPEA (Homarylamine) • MDOH • MDPR • MDPEA (Homopiperonylamine) • Mefenorex • Mephedrone • Mephentermine • Metanephrine • Metaraminol • Methamphetamine (Desoxyephedrine, Methedrine; Dextromethamphetamine, Levomethamphetamine) • Methoxamine • Methoxyphenamine • MMA • Methcathinone (Methylpropion) • Methedrone • Methoxyphenamine • Methylone • MMDA • MMDMA • MMMA • Morazone • N-Benzyl-1-phenethylamine • N,N-Dimethylphenethylamine • Naphthylamphetamine • Nisoxetine • Norepinephrine (Noradrenaline) • Norfenefrine • Norfenfluramine • Normetanephrine • Octopamine • Orciprenaline • Ortetamine • Oxilofrine • Paredrine (Norpholedrine, Oxamphetamine, Mycadrine) • PBA • PCA • PHA • Pargyline • Pentorex (Phenpentermine) • Pentylone • Phenatine • Phendimetrazine • Phenmetrazine • Phenpromethamine • Phentermine • Phenylalanine • Phenylephrine (Neosynephrine) • Phenylpropanolamine • Pholedrine • PIA • PMA • PMEA • PMMA • PPAP • Prenylamine • Propylamphetamine • Pseudoephedrine • Radafaxine • Ropinirole • Salbutamol (Albuterol; Levosalbutamol) • Sibutramine • Synephrine (Oxedrine) • Theodrenaline • Tiflorex (Flutiorex) • Tranylcypromine • Tyramine • Tyrosine • Xamoterol • Xylopropamine • Zylofuramine

Piperazines	2C-B-BZP • BZP • CM156 • DBL-583 • GBR-12783 • GBR-12935 • GBR-13069 • GBR-13098 • GBR-13119 • MeOPP • MBZP • Vanoxerine

Piperidines	1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine • 1-(3,4-Dichlorophenyl)-1-(piperidin-2-yl)butane • 2-Benzylpiperidine • 2-Methyl-3-phenylpiperidine • 3,4-Dichloromethylphenidate • 4-Benzylpiperidine • 4-Methylmethylphenidate • Desoxypipradrol • Difemetorex • Diphenylpyraline • Ethylphenidate • Methylnaphthidate • Methylphenidate (Dexmethylphenidate) • N-Methyl-3β-propyl-4β-(4-chlorophenyl)piperidine • Nocaine • Phacetoperane • Pipradrol • SCH-5472

Pyrrolidines	2-Diphenylmethylpyrrolidine • α-PPP • α-PBP • α-PVP • Diphenylprolinol • MDPPP • MDPBP • MDPV • MPBP • MPHP • MPPP • MOPPP • Naphyrone • PEP • Prolintane • Pyrovalerone

Tropanes	3-CPMT • 3'-Chloro-3α-(diphenylmethoxy)tropane • 3-Pseudotropyl-4-fluorobenzoate • 4'-Fluorococaine • AHN-1055 • Altropane (IACFT) • Brasofensine • CFT (WIN 35,428) • β-CIT (RTI-55) • Cocaethylene • Cocaine • Dichloropane (RTI-111) • Difluoropine • FE-β-CPPIT • FP-β-CPPIT • Ioflupane (¹²³I) • Norcocaine • PIT • PTT • RTI-31 • RTI-32 • RTI-51 • RTI-105 • RTI-112 • RTI-113 • RTI-117 • RTI-120 • RTI-121 (IPCIT) • RTI-126 • RTI-150 • RTI-154 • RTI-171 • RTI-177 • RTI-183 • RTI-193 • RTI-194 • RTI-199 • RTI-202 • RTI-204 • RTI-229 • RTI-241 • RTI-336 • RTI-354 • RTI-371 • RTI-386 • Salicylmethylecgonine • Tesofensine • Troparil (β-CPT, WIN 35,065-2) • Tropoxane • WF-23 • WF-33 • WF-60

Others	1-(Thiophen-2-yl)-2-aminopropane • 2-Amino-1,2-dihydronaphthalene • 2-Aminoindane • 2-Aminotetralin • 2-MDP • 2-Phenylcyclohexylamine • 2-Phenyl-3,6-dimethylmorpholine • 3-Benzhydrylmorpholine • 3,3-Diphenylcyclobutanamine • 5-(2-Aminopropyl)indole • 5-Iodo-2-aminoindane • AL-1095 • Amfonelic acid • Amineptine • Amiphenazole • Atipamezole • Atomoxetine (Tomoxetine) • Bemegride • Benzydamine • BTQ • BTS 74,398 • Carphedon • Ciclazindol • Cilobamine • Clofenciclan • Cropropamide • Crotetamide • Cypenamine • D-161 • Diclofensine • Dimethocaine • Efaroxan • Etamivan • EXP-561 • Fencamfamine • Fenpentadiol • Feprosidnine • G-130 • Gamfexine • Gilutensin • GSK1360707F • GYKI-52895 • Hexacyclonate • Idazoxan • Indanorex • Indatraline • JNJ-7925476 • JZ-IV-10 • Lazabemide • Leptacline • Levopropylhexedrine • Lomevactone • LR-5182 • Mazindol • Meclofenoxate • Medifoxamine • Mefexamide • Mesocarb • Methastyridone • Methiopropamine • N-Methyl-3-phenylnorbornan-2-amine • Nefopam • Nikethamide • Nomifensine • O-2172 • Oxaprotiline • Phthalimidopropiophenone • PNU-99,194 • Propylhexedrine • PRC200-SS • Rasagiline • Rauwolscine • Rubidium chloride • Setazindol • Tametraline • Tandamine • Trazium • UH-232 • Yohimbine

See also Sympathomimetic amines

Psychostimulants, agents used for ADHD, and nootropics (N06B)

Centrally acting sympathomimetics

Amphetamine • Amphetaminil • Atomoxetine • Dexmethylphenidate • Dextroamphetamine • Dextromethamphetamine • Fencamfamine • Fenethylline • Lisdexamfetamine • Methylphenidate • Mesocarb • Pemoline • Pipradrol • Prolintane

Xanthine derivatives

Caffeine • Fenethylline

Glutamate receptor

Racetams	Aniracetam • Nefiracetam • Noopept • Oxiracetam • Phenylpiracetam • Piracetam • Pramiracetam

Ampakines	CX-516 • CX-546 • CX-614 • CX-691 • CX-717 • IDRA-21 • LY-404,187 • LY-503,430 • PEPA • S-18986 • Sunifiram • Unifiram

Eugeroics / Benzhydryl compounds

Adrafinil • Armodafinil • Modafinil

Histamine H3 receptor antagonists

A-349,821 • ABT-239 • Ciproxifan • GSK-189,254

GABA_A α₅ inverse agonists

α₅IA • L-655,708 • PWZ-029 • Suritozole • TB-21007 • ZK-93426

Dopamine D1 receptor agonists

A-77636 • Dihydrexidine • Dinapsoline • Doxanthrine • SKF-81297 • 6-Br-APB

α7 nicotinic agonists / PAMs

AR-R17779 • PNU-282,987 • SSR-180,711

Prolyl endopeptidase inhibitors

S-17092

Alpha-adrenergic agonists

Clonidine • Guanfacine

Plants

Paullinia cupana (Guarana) • Eleutherococcus senticosus

Antioxidants

Stabilized R-(+)-lipoic acid (RLA)

Other psychostimulants and nootropics

Acetylcarnitine • Adafenoxate • Bifemelane • Carbenoxolone • Citicoline • Cyprodenate • Ensaculin • Idebenone • Ispronicline • Deanol • Dimebon • Fipexide • Leteprinim • Linopirdine • Meclofenoxate • Nizofenone • P7C3 • Pirisudanol • Pyritinol • Rubidium • Sulbutiamine • Taltirelin • Tricyanoaminopropene • Vinpocetine • Phosphatidylserine • Tyrosine

M: PSO/PSI

mepr

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

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

Adrenergics

Receptor ligands

α₁	Agonists: 5-FNE • 6-FNE • Amidephrine • Anisodamine • Anisodine • Cirazoline • Dipivefrine • Dopamine • Ephedrine • Epinephrine (Adrenaline) • Etilefrine • Ethylnorepinephrine • Indanidine • Levonordefrin • Metaraminol • Methoxamine • Methyldopa • Midodrine • Naphazoline • Norepinephrine (Noradrenaline) • Octopamine • Oxymetazoline • Phenylephrine • Phenylpropanolamine • Pseudoephedrine • Synephrine • Tetrahydrozoline Antagonists: Abanoquil • Adimolol • Ajmalicine • Alfuzosin • Amosulalol • Arotinolol • Atiprosin • Benoxathian • Buflomedil • Bunazosin • Carvedilol • CI-926 • Corynanthine • Dapiprazole • DL-017 • Domesticine • Doxazosin • Eugenodilol • Fenspiride • GYKI-12,743 • GYKI-16,084 • Indoramin • Ketanserin • L-765,314 • Labetalol • Mephendioxan • Metazosin • Monatepil • Moxisylyte (Thymoxamine) • Naftopidil • Nantenine • Neldazosin • Nicergoline • Niguldipine • Pelanserin • Phendioxan • Phenoxybenzamine • Phentolamine • Piperoxan • Prazosin • Quinazosin • Ritanserin • RS-97,078 • SGB-1,534 • Silodosin • SL-89.0591 • Spiperone • Talipexole • Tamsulosin • Terazosin • Tibalosin • Tiodazosin • Tipentosin • Tolazoline • Trimazosin • Upidosin • Urapidil • Zolertine * Note that many TCAs, TeCAs, antipsychotics, ergolines, and some piperazines like buspirone, trazodone, nefazodone, etoperidone, and mepiprazole all antagonize α₁-adrenergic receptors as well, which contributes to their side effects such as orthostatic hypotension.

α₂	Agonists: (R)-3-Nitrobiphenyline • 4-NEMD • 6-FNE • Amitraz • Apraclonidine • Brimonidine • Cannabivarin • Clonidine • Detomidine • Dexmedetomidine • Dihydroergotamine • Dipivefrine • Dopamine • Ephedrine • Ergotamine • Epinephrine (Adrenaline) • Esproquin • Etilefrine • Ethylnorepinephrine • Guanabenz • Guanfacine • Guanoxabenz • Levonordefrin • Lofexidine • Medetomidine • Methyldopa • Mivazerol • Naphazoline • Norepinephrine (Noradrenaline) • Phenylpropanolamine • Piperoxan • Pseudoephedrine • Rilmenidine • Romifidine • Talipexole • Tetrahydrozoline • Tizanidine • Tolonidine • Urapidil • Xylazine • Xylometazoline Antagonists: 1-PP • Adimolol • Aptazapine • Atipamezole • BRL-44408 • Buflomedil • Cirazoline • Efaroxan • Esmirtazapine • Fenmetozole • Fluparoxan • GYKI-12,743 • GYKI-16,084 • Idazoxan • Mianserin • Mirtazapine • MK-912 • NAN-190 • Olanzapine • Phentolamine • Phenoxybenzamine • Piperoxan • Piribedil • Rauwolscine • Rotigotine • SB-269,970 • Setiptiline • Spiroxatrine • Sunepitron • Tolazoline • Yohimbine * Note that many atypical antipsychotics and azapirones like buspirone and gepirone (via metabolite 1-PP) antagonize α₂-adrenergic receptors as well.

β	Agonists: 2-FNE • 5-FNE • Amibegron • Arbutamine • Arformoterol • Arotinolol • BAAM • Bambuterol • Befunolol • Bitolterol • Broxaterol • Buphenine • Carbuterol • Cimaterol • Clenbuterol • Denopamine • Deterenol • Dipivefrine • Dobutamine • Dopamine • Dopexamine • Ephedrine • Epinephrine (Adrenaline) • Etafedrine • Etilefrine • Ethylnorepinephrine • Fenoterol • Formoterol • Hexoprenaline • Higenamine • Indacaterol • Isoetarine • Isoprenaline (Isoproterenol) • Isoxsuprine • Labetalol • Levonordefrin • Levosalbutamol • Mabuterol • Methoxyphenamine • Methyldopa • N-Isopropyloctopamine • Norepinephrine (Noradrenaline) • Orciprenaline • Oxyfedrine • Phenylpropanolamine • Pirbuterol • Prenalterol • Ractopamine • Procaterol • Pseudoephedrine • Reproterol • Rimiterol • Ritodrine • Salbutamol (Albuterol) • Salmeterol • Solabegron • Terbutaline • Tretoquinol • Tulobuterol • Xamoterol • Zilpaterol • Zinterol Antagonists: Acebutolol • Adaprolol • Adimolol • Afurolol • Alprenolol • Alprenoxime • Amosulalol • Ancarolol • Arnolol • Arotinolol • Atenolol • Befunolol • Betaxolol • Bevantolol • Bisoprolol • Bopindolol • Bormetolol • Bornaprolol • Brefonalol • Bucindolol • Bucumolol • Bufetolol • Buftiralol • Bufuralol • Bunitrolol • Bunolol • Bupranolol • Burocrolol • Butaxamine • Butidrine • Butofilolol • Capsinolol • Carazolol • Carpindolol • Carteolol • Carvedilol • Celiprolol • Cetamolol • Cicloprolol • Cinamolol • Cloranolol • Cyanopindolol • Dalbraminol • Dexpropranolol • Diacetolol • Dichloroisoprenaline • Dihydroalprenolol • Dilevalol • Diprafenone • Draquinolol • Dropranolol • Ecastolol • Epanolol • Ericolol • Ersentilide • Esatenolol • Esmolol • Esprolol • Eugenodilol • Exaprolol • Falintolol • Flestolol • Flusoxolol • Hydroxycarteolol • Hydroxytertatolol • ICI-118,551 • Idropranolol • Indenolol • Indopanolol • Iodocyanopindolol • Iprocrolol • Isoxaprolol • Isamoltane • Labetalol • Landiolol • Levobetaxolol • Levobunolol • Levocicloprolol • Levomoprolol • Medroxalol • Mepindolol • Metalol • Metipranolol • Metoprolol • Moprolol • Nadolol • Nadoxolol • Nafetolol • Nebivolol • Neraminol • Nifenalol • Nipradilol • Oberadilol • Oxprenolol • Pacrinolol • Pafenolol • Pamatolol • Pargolol • Parodilol • Penbutolol • Penirolol • PhQA-33 • Pindolol • Pirepolol • Practolol • Primidolol • Procinolol • Pronethalol • Propafenone • Propranolol • Ridazolol • Ronactolol • Soquinolol • Sotalol • Spirendolol • SR 59230A • Sulfinalol • TA-2005 • Talinolol • Tazolol • Teoprolol • Tertatolol • Terthianolol • Tienoxolol • Tilisolol • Timolol • Tiprenolol • Tolamolol • Toliprolol • Tribendilol • Trigevolol • Xibenolol • Xipranolol

Reuptake inhibitors

NET	Selective norepinephrine reuptake inhibitors: Amedalin • Atomoxetine (Tomoxetine) • Ciclazindol • Daledalin • Esreboxetine • Lortalamine • Mazindol • Nisoxetine • Reboxetine • Talopram • Talsupram • Tandamine • Viloxazine; Norepinephrine-dopamine reuptake inhibitors: Amineptine • Bupropion (Amfebutamone) • Fencamine • Fencamfamine • Lefetamine • Levophacetoperane • LR-5182 • Manifaxine • Methylphenidate • Nomifensine • O-2172 • Radafaxine; Serotonin-norepinephrine reuptake inhibitors: Bicifadine • Desvenlafaxine • Duloxetine • Eclanamine • Levomilnacipran • Milnacipran • Sibutramine • Venlafaxine; Serotonin-norepinephrine-dopamine reuptake inhibitors: Brasofensine • Diclofensine • DOV-102,677 • DOV-21,947 • DOV-216,303 • JNJ-7925476 • JZ-IV-10 • Methylnaphthidate • Naphyrone • NS-2359 • PRC200-SS • SEP-225,289 • SEP-227,162 • Tesofensine; Tricyclic antidepressants: Amitriptyline • Butriptyline • Cianopramine • Clomipramine • Desipramine • Dosulepin • Doxepin • Imipramine • Lofepramine • melitracen • Nortriptyline • Protriptyline • Trimipramine; Tetracyclic antidepressants: Amoxapine • Maprotiline • Mianserin • Oxaprotiline • Setiptiline; Others: Cocaine • CP-39,332 • EXP-561 • Fezolamine • Ginkgo biloba • Indeloxazine • Nefazodone • Nefopam • Pridefrine • Tapentadol • Tedatioxetine • Teniloxazine • Tramadol • Ziprasidone

VMAT	Ibogaine • Reserpine • Tetrabenazine

Releasing agents

Morpholines: Fenbutrazate • Morazone • Phendimetrazine • Phenmetrazine; Oxazolines: 4-Methylaminorex • Aminorex • Clominorex • Cyclazodone • Fenozolone • Fluminorex • Pemoline • Thozalinone; Phenethylamines (also amphetamines, cathinones, phentermines, etc): 2-OH-PEA • 4-CAB • 4-FA • 4-FMA • 4-MA • 4-MMA • Alfetamine • Amfecloral • Amfepentorex • Amfepramone • Amphetamine (Dextroamphetamine, Levoamphetamine) • Amphetaminil • β-Me-PEA • BDB • Benzphetamine • BOH • Buphedrone • Butylone • Cathine • Cathinone • Clobenzorex • Clortermine • D-Deprenyl • Dimethylamphetamine • Dimethylcathinone (Dimethylpropion, metamfepramone) • DMA • DMMA • EBDB • Ephedrine • Ethcathinone • Ethylamphetamine • Ethylone • Famprofazone • Fenethylline • Fenproporex • Flephedrone • Fludorex • Furfenorex • Hordenine • IAP • IMP • L-Deprenyl (Selegiline) • Lisdexamfetamine • Lophophine • MBDB • MDA (Tenamfetamine) • MDEA • MDMA • MDMPEA • MDOH • MDPEA • Mefenorex • Mephedrone • Mephentermine • Methamphetamine (Dextromethamphetamine, Levomethamphetamine) • Methcathinone • Methedrone • Methylone • NAP • Ortetamine • Paredrine • pBA • pCA • Pentorex (Phenpentermine) • Phenethylamine • Pholedrine • Phenpromethamine • Phentermine • Phenylpropanolamine • pIA • Prenylamine • Propylamphetamine • Pseudoephedrine • Tiflorex • Tyramine • Xylopropamine • Zylofuramine; Piperazines: 2C-B-BZP • BZP • MBZP • mCPP • MDBZP • MeOPP • pFPP; Others: 2-Amino-1,2-dihydronaphthalene • 2-Aminoindane • 2-Aminotetralin • 2-Benzylpiperidine • 4-Benzylpiperidine • 5-IAI • Clofenciclan • Cyclopentamine • Cypenamine • Cyprodenate • Feprosidnine • Gilutensin • Heptaminol • Hexacyclonate • Indanorex • Isometheptene • Methylhexanamine • Octodrine • Phthalimidopropiophenone • Propylhexedrine (Levopropylhexedrine) • Tuaminoheptane

Enzyme inhibitors

Anabolism

PAH	3,4-Dihydroxystyrene

TH	3-Iodotyrosine • Aquayamycin • Bulbocapnine • Metirosine • Oudenone

AAAD	Benserazide • Carbidopa • Genistein • Methyldopa

DBH	Bupicomide • Disulfiram • Dopastin • Fusaric acid • Nepicastat • Phenopicolinic acid • Tropolone

PNMT	CGS-19281A • SKF-64139 • SKF-7698

Catabolism

MAO	Nonselective: Benmoxin • Caroxazone • Echinopsidine • Furazolidone • Hydralazine • Indantadol • Iproclozide • Iproniazid • Isocarboxazid • Isoniazid • Linezolid • Mebanazine • Metfendrazine • Nialamide • Octamoxin • Paraxazone • Phenelzine • Pheniprazine • Phenoxypropazine • Pivalylbenzhydrazine • Procarbazine • Safrazine • Tranylcypromine; MAO-A selective: Amiflamine • Bazinaprine • Befloxatone • Befol • Brofaromine • Cimoxatone • Clorgiline • Esuprone • Harmala alkaloids (Harmine, Harmaline, Tetrahydroharmine, Harman, Norharman, etc) • Methylene Blue • Metralindole • Minaprine • Moclobemide • Pirlindole • Sercloremine • Tetrindole • Toloxatone • Tyrima; MAO-B selective: D-Deprenyl • Selegiline (L-Deprenyl) • Ladostigil • Lazabemide • Milacemide • Mofegiline • Pargyline • Rasagiline • Safinamide * Note that MAO-B inhibitors also influence norepinephrine/epinephrine levels since they inhibit the breakdown of their precursor dopamine.

COMT	Entacapone • Tolcapone

Others

Precursors	L-Phenylalanine → L-Tyrosine → L-DOPA (Levodopa) → Dopamine • L-DOPS (Droxidopa)

Cofactors	Ferrous Iron (Fe²⁺) • S-Adenosyl-L-Methionine • Vitamin B₃ (Niacin, Nicotinamide → NADPH) • Vitamin B₆ (Pyridoxine, Pyridoxamine, Pyridoxal → Pyridoxal Phosphate) • Vitamin B₉ (Folic acid → Tetrahydrofolic acid) • Vitamin C (Ascorbic acid) • Zinc (Zn²⁺)

Others	Activity enhancers: BPAP • PPAP; Release blockers: Bethanidine • Bretylium • Guanadrel • Guanazodine • Guanclofine • Guanethidine • Guanoxan; Toxins: Oxidopamine (6-Hydroxydopamine)

List of adrenergic drugs

Dopaminergics