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Identification
NameTalampanel
Accession NumberDB04982
TypeSmall Molecule
GroupsInvestigational
DescriptionTalampanel is a substance that is being studied in the treatment of brain tumors and other brain disorders, such as epilepsy and Parkinson disease. It is a type of AMPA receptor antagonist.
Structure
Thumb
SynonymsNot Available
External Identifiers
  • LY300164
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AmpanelNot Available
KinampaNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIICVS43XG1L5
CAS number161832-65-1
WeightAverage: 337.3725
Monoisotopic: 337.142641489
Chemical FormulaC19H19N3O3
InChI KeyJACAAXNEHGBPOQ-LLVKDONJSA-N
InChI
InChI=1S/C19H19N3O3/c1-11-7-14-8-17-18(25-10-24-17)9-16(14)19(21-22(11)12(2)23)13-3-5-15(20)6-4-13/h3-6,8-9,11H,7,10,20H2,1-2H3/t11-/m1/s1
IUPAC Name
1-[(13R)-10-(4-aminophenyl)-13-methyl-4,6-dioxa-11,12-diazatricyclo[7.5.0.0³,⁷]tetradeca-1,3(7),8,10-tetraen-12-yl]ethan-1-one
SMILES
C[C@@H]1CC2=CC3=C(OCO3)C=C2C(=NN1C(C)=O)C1=CC=C(N)C=C1
Pharmacology
IndicationFor the treatment of epilepsy.
Structured Indications Not Available
PharmacodynamicsTalampanel, a potent and selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-receptor antagonist, is a potential new antiepileptic drug (AED). Talampanel dosing strategies may be reliant on concomitant AED medication, as enzyme-inducing AEDs enhance, whereas VPA inhibits its metabolism. Talampanel was well tolerated, although adverse events occurred at lower doses compared with those in healthy subjects, probably because of the additive effect of concomitant AEDs.
Mechanism of actionTalampanel is a potent noncompetitive and selective antagonist of the glutamine AMPA receptors. Studies in primates have shown that the administration of talampanel to parkinsonian monkeys significantly decreased levodopa-induced dyskinesias by 40%. When given alone, talampanel did not modify the severity of parkinsonian symptoms. However, in combination with levodopa, talampanel potentiated the antiparkinsonian action of levodopa by increasing motor activity.
TargetKindPharmacological actionActionsOrganismUniProt ID
Glutamate receptor 1ProteinunknownNot AvailableHumanP42261 details
Glutamate receptor 2ProteinunknownNot AvailableHumanP42262 details
Glutamate receptor 3ProteinunknownNot AvailableHumanP42263 details
Glutamate receptor 4ProteinunknownNot AvailableHumanP48058 details
Related Articles
AbsorptionRapidly absorbed, with maximal plasma concentrations achieved within 1-3 hours.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life3-6 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Langan YM, Lucas R, Jewell H, Toublanc N, Schaefer H, Sander JW, Patsalos PN: Talampanel, a new antiepileptic drug: single- and multiple-dose pharmacokinetics and initial 1-week experience in patients with chronic intractable epilepsy. Epilepsia. 2003 Jan;44(1):46-53. [PubMed:12581229 ]
  2. Konitsiotis S, Blanchet PJ, Verhagen L, Lamers E, Chase TN: AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys. Neurology. 2000 Apr 25;54(8):1589-95. [PubMed:10762498 ]
  3. Erdo F, Berzsenyi P, Nemet L, Andrasi F: Talampanel improves the functional deficit after transient focal cerebral ischemia in rats. A 30-day follow up study. Brain Res Bull. 2006 Jan 15;68(4):269-76. Epub 2005 Sep 19. [PubMed:16377432 ]
  4. Buchwald P, Juhasz A, Bell C, Patfalusi M, Howes J, Bodor N: Unified pharmacogenetics-based parent-metabolite pharmacokinetic model incorporating acetylation polymorphism for talampanel in humans. J Pharmacokinet Pharmacodyn. 2005 Aug;32(3-4):377-400. [PubMed:16320099 ]
  5. Belayev L, Alonso OF, Liu Y, Chappell AS, Zhao W, Ginsberg MD, Busto R: Talampanel, a novel noncompetitive AMPA antagonist, is neuroprotective after traumatic brain injury in rats. J Neurotrauma. 2001 Oct;18(10):1031-8. [PubMed:11686490 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9604
Caco-2 permeable+0.5108
P-glycoprotein substrateNon-substrate0.6808
P-glycoprotein inhibitor INon-inhibitor0.6984
P-glycoprotein inhibitor IIInhibitor0.6921
Renal organic cation transporterNon-inhibitor0.8149
CYP450 2C9 substrateNon-substrate0.8327
CYP450 2D6 substrateNon-substrate0.8135
CYP450 3A4 substrateSubstrate0.7208
CYP450 1A2 substrateInhibitor0.7402
CYP450 2C9 inhibitorInhibitor0.7333
CYP450 2D6 inhibitorNon-inhibitor0.7342
CYP450 2C19 inhibitorInhibitor0.7168
CYP450 3A4 inhibitorInhibitor0.589
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9152
Ames testNon AMES toxic0.5
CarcinogenicityNon-carcinogens0.6491
BiodegradationNot ready biodegradable0.9881
Rat acute toxicity2.7049 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9984
hERG inhibition (predictor II)Non-inhibitor0.8278
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.126 mg/mLALOGPS
logP1.97ALOGPS
logP2.33ChemAxon
logS-3.4ALOGPS
pKa (Strongest Basic)3.38ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area77.15 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity94.65 m3·mol-1ChemAxon
Polarizability36.34 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzodioxoles. These are organic compounds containing a benzene ring fused to either isomers of dioxole. Dioxole is a five-membered unsaturated ring of two oxygen atoms and three carbon atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodioxoles
Sub ClassNot Available
Direct ParentBenzodioxoles
Alternative Parents
Substituents
  • Benzodioxole
  • Substituted aniline
  • Aniline
  • Benzenoid
  • Primary aromatic amine
  • Monocyclic benzene moiety
  • Acetamide
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Carboxylic acid derivative
  • Acetal
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Pdz domain binding
Specific Function:
Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inacti...
Gene Name:
GRIA1
Uniprot ID:
P42261
Molecular Weight:
101505.245 Da
References
  1. Langan YM, Lucas R, Jewell H, Toublanc N, Schaefer H, Sander JW, Patsalos PN: Talampanel, a new antiepileptic drug: single- and multiple-dose pharmacokinetics and initial 1-week experience in patients with chronic intractable epilepsy. Epilepsia. 2003 Jan;44(1):46-53. [PubMed:12581229 ]
  2. Howes JF, Bell C: Talampanel. Neurotherapeutics. 2007 Jan;4(1):126-9. [PubMed:17199027 ]
  3. Denes L, Szilagyi G, Gal A, Nagy Z: Talampanel a non-competitive AMPA-antagonist attenuates caspase-3 dependent apoptosis in mouse brain after transient focal cerebral ischemia. Brain Res Bull. 2006 Jul 31;70(3):260-2. Epub 2006 Mar 31. [PubMed:16861112 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Ionotropic glutamate receptor activity
Specific Function:
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and t...
Gene Name:
GRIA2
Uniprot ID:
P42262
Molecular Weight:
98820.32 Da
References
  1. Langan YM, Lucas R, Jewell H, Toublanc N, Schaefer H, Sander JW, Patsalos PN: Talampanel, a new antiepileptic drug: single- and multiple-dose pharmacokinetics and initial 1-week experience in patients with chronic intractable epilepsy. Epilepsia. 2003 Jan;44(1):46-53. [PubMed:12581229 ]
  2. Howes JF, Bell C: Talampanel. Neurotherapeutics. 2007 Jan;4(1):126-9. [PubMed:17199027 ]
  3. Denes L, Szilagyi G, Gal A, Nagy Z: Talampanel a non-competitive AMPA-antagonist attenuates caspase-3 dependent apoptosis in mouse brain after transient focal cerebral ischemia. Brain Res Bull. 2006 Jul 31;70(3):260-2. Epub 2006 Mar 31. [PubMed:16861112 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Extracellular-glutamate-gated ion channel activity
Specific Function:
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and t...
Gene Name:
GRIA3
Uniprot ID:
P42263
Molecular Weight:
101155.975 Da
References
  1. Langan YM, Lucas R, Jewell H, Toublanc N, Schaefer H, Sander JW, Patsalos PN: Talampanel, a new antiepileptic drug: single- and multiple-dose pharmacokinetics and initial 1-week experience in patients with chronic intractable epilepsy. Epilepsia. 2003 Jan;44(1):46-53. [PubMed:12581229 ]
  2. Howes JF, Bell C: Talampanel. Neurotherapeutics. 2007 Jan;4(1):126-9. [PubMed:17199027 ]
  3. Denes L, Szilagyi G, Gal A, Nagy Z: Talampanel a non-competitive AMPA-antagonist attenuates caspase-3 dependent apoptosis in mouse brain after transient focal cerebral ischemia. Brain Res Bull. 2006 Jul 31;70(3):260-2. Epub 2006 Mar 31. [PubMed:16861112 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Ionotropic glutamate receptor activity
Specific Function:
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and t...
Gene Name:
GRIA4
Uniprot ID:
P48058
Molecular Weight:
100870.085 Da
References
  1. Langan YM, Lucas R, Jewell H, Toublanc N, Schaefer H, Sander JW, Patsalos PN: Talampanel, a new antiepileptic drug: single- and multiple-dose pharmacokinetics and initial 1-week experience in patients with chronic intractable epilepsy. Epilepsia. 2003 Jan;44(1):46-53. [PubMed:12581229 ]
  2. Howes JF, Bell C: Talampanel. Neurotherapeutics. 2007 Jan;4(1):126-9. [PubMed:17199027 ]
  3. Denes L, Szilagyi G, Gal A, Nagy Z: Talampanel a non-competitive AMPA-antagonist attenuates caspase-3 dependent apoptosis in mouse brain after transient focal cerebral ischemia. Brain Res Bull. 2006 Jul 31;70(3):260-2. Epub 2006 Mar 31. [PubMed:16861112 ]
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Drug created on October 21, 2007 16:23 / Updated on August 17, 2016 12:24