DT-Web

DB06218 - Lacosamide


Identification
Name Lacosamide
Accession Number DB06218
Type small molecule
Description Lacosamide is a functionalized amino acid that has activity in the maximal electroshock seizure test, and is indicated for the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain. Recent studies indicate that Lacosamide only affects those neurons which are depolarized or active for long periods of time, typical of neurons at the focus of an epileptic seizure, as opposed to other antiepileptic drugs such as carbamazepine or lamotrigine which slow the recovery from inactivation and reduce the ability of neurons to fire action potentials.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 250.2936
Groups approved
Monoisotopic Weight 250.131742452
Pharmacology
Indication Lacosamide is indicated for adjunctive therapy for partial onset seizures in patients with epilepsy over 17 years old. Injection is indicated for short term use when oral therapy is not feasible.
Mechanism of action It is proposed that lacosamide's inhibition of sodium channels is responsible for analgesia. Lacosamide may be selective for inhibiting depolarized neurons rather than neurons with normal resting potentials. Pain and nociceptor hyperexcitability are associated with neural membrane depolarization. Lacosamide binds to collapsin response mediator protein-2 (CRMP-2), a phosphoprotein which is expressed primarily in the nervous system and is involved in neuronal differentiation and control of axonal outgrowth. The role CRMP-2 of binding in seizure control is hasn't been elucidated.
Absorption Lacosamide has a negligible first pass effect with bioavailability of about 100%. The maximum Lacosamide plasma concentrations occur about 1-4 hours after oral administration, and the pharmacokinetics of Lacosamide are dose proportional. Food does not affect absorption.
Protein binding <15%
Biotransformation Lacosamide is a CYP2C19 substrate. The relative contribution of other CYP isoforms or non-CYP enzymes in the metabolism of lacosamide is not known. Primary compounds excreted were unchanged lacosamide (approximately 40% of the dose), its O-desmethyl metabolite (approximately 30%), and a structurally unknown polar fraction (~20%). The plasma exposure of the major human metabolite, O-desmethyl-lacosamide, is approximately 10% of that of lacosamide. This metabolite has no known pharmacological activity.
Route of elimination Lacosamide is eliminated primarily from the systemic circulation by biotransformation and renal excretion.
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Valproic Acid Valproic acid toxicity may occur at any time during the treatment course and should be considered in patients with acute changes in mentation, especially if there has been a recent change in antiepileptic therapy.
Food Interactions Not Available

Targets


Sodium channel protein type 9 subunit alpha
Name Sodium channel protein type 9 subunit alpha
Gene Name SCN9A
Pharmacological action unknown
Actions Not Available
References Not Available
DTHybrid score 0.5266
Sodium channel protein type 3 subunit alpha
Name Sodium channel protein type 3 subunit alpha
Gene Name SCN3A
Pharmacological action unknown
Actions Not Available
References
  • Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. - Pubmed
DTHybrid score 0.477
Sodium channel protein type 10 subunit alpha
Name Sodium channel protein type 10 subunit alpha
Gene Name SCN10A
Pharmacological action unknown
Actions Not Available
References
  • Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. - Pubmed
DTHybrid score 0.8043

Predictions


Id Partner name Gene Name Score
220 Sodium channel protein type 5 subunit alpha SCN5A 0.1272
4512 Cytochrome P450 3A4 CYP3A4 0.0832
3923 Cholinesterase BCHE 0.0576
4604 Liver carboxylesterase 1 CES1 0.051
4119 Cytochrome P450 2D6 CYP2D6 0.0506
2178 Metabotropic glutamate receptor 5 GRM5 0.0486
4200 Cytochrome P450 1A2 CYP1A2 0.0378
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0357
6135 Sodium channel subunit beta-4 SCN4B 0.0354
6133 Sodium channel subunit beta-2 SCN2B 0.0354
6134 Sodium channel subunit beta-3 SCN3B 0.0354
6132 Sodium channel subunit beta-1 SCN1B 0.0354
6129 Carbonic anhydrase-related protein 11 CA11 0.0354
6127 Carbonic anhydrase-related protein CA8 0.0354
6128 Carbonic anhydrase-related protein 10 CA10 0.0354
6124 Carbonic anhydrase 5B, mitochondrial CA5B 0.0311
6130 Carbonic anhydrase 13 CA13 0.0307
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0296
3802 Sodium channel protein type 2 subunit alpha SCN2A 0.0295
6131 Carbonic anhydrase 14 CA14 0.0271
6122 Carbonic anhydrase 3 CA3 0.0266
6123 Carbonic anhydrase 5A, mitochondrial CA5A 0.0254
713 Sodium-dependent dopamine transporter SLC6A3 0.0249
3804 Sodium channel protein type 4 subunit alpha SCN4A 0.0249
6013 Cytochrome P450 2E1 CYP2E1 0.0245
6030 Cytochrome P450 2B6 CYP2B6 0.0244
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0236
4205 Carbonic anhydrase 9 CA9 0.023
3007 Carbonic anhydrase 12 CA12 0.023
341 5-hydroxytryptamine 3 receptor HTR3A 0.0229
1588 Multidrug resistance protein 1 ABCB1 0.0216
6126 Carbonic anhydrase 7 CA7 0.0216
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0212
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0201
587 Serum albumin ALB 0.0201
844 Epidermal growth factor receptor EGFR 0.0197
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.019
6020 Aldehyde oxidase AOX1 0.0172
6016 Cytochrome P450 2C19 CYP2C19 0.017
592 Carbonic anhydrase 4 CA4 0.0166
465 Calmodulin CALM1 0.0163
295 Carbonic anhydrase 1 CA1 0.0159
3939 Amine oxidase [flavin-containing] B MAOB 0.0159
3941 Amine oxidase [flavin-containing] A MAOA 0.0154
6106 Cytochrome P450 2C18 CYP2C18 0.014
73 Prostaglandin E2 receptor, EP1 subtype PTGER1 0.014
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0138
357 Carbonic anhydrase 2 CA2 0.0137
6107 Cytochrome P450 3A7 CYP3A7 0.0132
4118 Cytochrome P450 3A5 CYP3A5 0.0125
4924 Cytochrome P450 2C8 CYP2C8 0.0124
118 Organic cation/carnitine transporter 2 SLC22A5 0.0121
5718 Cytochrome P450 2A6 CYP2A6 0.0116
4757 Cytochrome P450 2C9 CYP2C9 0.0115
813 Neuronal acetylcholine receptor subunit alpha-2 CHRNA2 0.0108
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0095
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0091
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0083
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.008
492 Histamine H1 receptor HRH1 0.0051
824 Sodium-dependent serotonin transporter SLC6A4 0.0038
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0036
6144 Solute carrier family 22 member 2 SLC22A2 0.0035
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0034
↑