DT-Web

DB01255 - Lisdexamfetamine


Identification
Name Lisdexamfetamine
Accession Number DB01255
Type small molecule
Description Lisdexamfetamine (L-lysine-d-amphetamine) is a prodrug of the psychostimulant d-amphetamine coupled with the essential amino acid L-lysine. It was developed so that the amphetamine psychostimulant is released and activated more slowly as the prodrug molecule is hydrolyzed consequently cleaving off the amino acid-during the first pass through the intestines and/or the liver. Amphetamines target the trace amine-associated receptor 1 (TAAR1). Amphetamine is also believed to exert its effects by binding to the monoamine transporters (the dopamine transporter or DAT) and increasing extracellular levels of the biogenic amines dopamine, norepinephrine (noradrenaline) and serotonin.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 263.3785
Groups approved
Monoisotopic Weight 263.199762437
Pharmacology
Indication For the treatment of Attention Deficit/Hyperactivity Disorder (ADHD) in pediatric populations aged 6 to 12 years.
Mechanism of action Lisdexamfetamine is a pro-drug of dextroamphetamine. 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. Norepinephrine and dopamine contribute to maintaining alertness, increasing focus, and sustaining thought, effort, and motivation. However, the exact therapeutic action in ADHD is not known.
Absorption After oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract.
Protein binding Not Available
Biotransformation Lisdexamfetamine is converted to dextroamphetamine and L-lysine, which is believed to occur by first-pass intestinal and/or hepatic metabolism. Lisdexamfetamine is not metabolized by cytochrome P450 enzymes.
Route of elimination Not Available
Toxicity Manifestations of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia and rhabdomyolysis. Fatigue and depression usually follow the central nervous system stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trandolapril Lisdexamfetamine may reduce the efficacy of Trandolapril.
Tranylcypromine The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the amphetamine, Lisdexamfetamine. Concomitant therapy should be avoided.
Triprolidine Triprolidine may reduce the sedative effect of the antihistamine, Lisdexamfetamine.
Food Interactions Not Available

Targets


Sodium-dependent dopamine transporter
Name Sodium-dependent dopamine transporter
Gene Name SLC6A3
Pharmacological action yes
Actions inhibitor
References
  • Hamidovic A, Dlugos A, Palmer AA, de Wit H: Polymorphisms in dopamine transporter (SLC6A3) are associated with stimulant effects of D-amphetamine: an exploratory pharmacogenetic study using healthy volunteers. Behav Genet. 2010 Mar;40(2):255-61. Epub 2010 Jan 21. - Pubmed
DTHybrid score 0.3756
Alpha-1B adrenergic receptor
Name Alpha-1B adrenergic receptor
Gene Name ADRA1B
Pharmacological action unknown
Actions antagonist
References
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.2144

Predictions


Id Partner name Gene Name Score
540 Sodium-dependent noradrenaline transporter SLC6A2 0.1556
556 Alpha-1A adrenergic receptor ADRA1A 0.1345
824 Sodium-dependent serotonin transporter SLC6A4 0.0934
4119 Cytochrome P450 2D6 CYP2D6 0.0806
789 Alpha-1D adrenergic receptor ADRA1D 0.073
318 Alpha-2A adrenergic receptor ADRA2A 0.0517
4512 Cytochrome P450 3A4 CYP3A4 0.0495
131 Synaptic vesicular amine transporter SLC18A2 0.0473
492 Histamine H1 receptor HRH1 0.0432
502 5-hydroxytryptamine 2A receptor HTR2A 0.0427
23 D(1A) dopamine receptor DRD1 0.0383
3941 Amine oxidase [flavin-containing] A MAOA 0.0381
629 Alpha-2B adrenergic receptor ADRA2B 0.0356
4200 Cytochrome P450 1A2 CYP1A2 0.0341
831 D(2) dopamine receptor DRD2 0.0326
6016 Cytochrome P450 2C19 CYP2C19 0.0294
3939 Amine oxidase [flavin-containing] B MAOB 0.0284
378 Alpha-2C adrenergic receptor ADRA2C 0.0279
590 5-hydroxytryptamine 2C receptor HTR2C 0.0271
1588 Multidrug resistance protein 1 ABCB1 0.0264
320 5-hydroxytryptamine 1A receptor HTR1A 0.0259
1636 Trace amine-associated receptor 1 TAAR1 0.0255
4757 Cytochrome P450 2C9 CYP2C9 0.0243
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0222
6030 Cytochrome P450 2B6 CYP2B6 0.0188
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0186
193 Beta-1 adrenergic receptor ADRB1 0.0184
432 D(4) dopamine receptor DRD4 0.0179
4118 Cytochrome P450 3A5 CYP3A5 0.017
766 Beta-2 adrenergic receptor ADRB2 0.0168
341 5-hydroxytryptamine 3 receptor HTR3A 0.0168
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0165
6145 Solute carrier family 22 member 1 SLC22A1 0.0162
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0153
638 D(3) dopamine receptor DRD3 0.0137
725 5-hydroxytryptamine 1D receptor HTR1D 0.013
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0128
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0128
6147 Solute carrier family 22 member 3 SLC22A3 0.0122
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0122
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0117
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0116
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0113
6144 Solute carrier family 22 member 2 SLC22A2 0.0112
3923 Cholinesterase BCHE 0.0109
118 Organic cation/carnitine transporter 2 SLC22A5 0.0106
163 D(1B) dopamine receptor DRD5 0.0106
6107 Cytochrome P450 3A7 CYP3A7 0.0103
1656 CYP2B protein CYP2B 0.0101
51 Muscarinic acetylcholine receptor M3 CHRM3 0.01
885 5-hydroxytryptamine 1B receptor HTR1B 0.0095
982 Cocaine- and amphetamine-regulated transcript protein CARTPT 0.0095
436 5-hydroxytryptamine 2B receptor HTR2B 0.0094
6013 Cytochrome P450 2E1 CYP2E1 0.0094
1256 5-hydroxytryptamine 6 receptor HTR6 0.0093
1517 Beta-3 adrenergic receptor ADRB3 0.0088
587 Serum albumin ALB 0.008
828 Phenylalanine-4-hydroxylase PAH 0.0074
3109 Phenylalanine-4-hydroxylase phhA 0.0074
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0073
6138 Multidrug resistance protein 3 ABCB4 0.007
716 5-hydroxytryptamine 7 receptor HTR7 0.0067
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0064
5718 Cytochrome P450 2A6 CYP2A6 0.0064
4924 Cytochrome P450 2C8 CYP2C8 0.0064
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0061
528 5-hydroxytryptamine 1E receptor HTR1E 0.006
1757 Myeloperoxidase MPO 0.006
813 Neuronal acetylcholine receptor subunit alpha-2 CHRNA2 0.0057
4120 NADPH--cytochrome P450 reductase POR 0.0057
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0043
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.004
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0039
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0038
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0028
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0028
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0028
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0028
153 Dopamine beta-hydroxylase DBH 0.0025
6024 Cytochrome P450 1A1 CYP1A1 0.0023
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0022
233 Potassium channel subfamily K member 2 KCNK2 0.0022
6151 Monocarboxylate transporter 10 SLC16A10 0.002
3810 Catechol O-methyltransferase COMT 0.002
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.002
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0019
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0019
6047 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A PDE1A 0.0018
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0017
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0017
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0017
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0017
776 Bile salt export pump ABCB11 0.0016
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0015
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0014
465 Calmodulin CALM1 0.0013
124 Histamine H2 receptor HRH2 0.0012
164 Histamine H4 receptor HRH4 0.0012
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0012
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0009
1898 Cytochrome P450 1B1 CYP1B1 0.0007
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