NAV

Talampanel

Identification

Generic Name
Talampanel
DrugBank Accession Number
DB04982
Background

Talampanel 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.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 337.3725
Monoisotopic: 337.142641489
Chemical Formula
C19H19N3O3
Synonyms
  • Talampanel
External IDs
  • GYKI 53405
  • GYKI-53773
  • LY-300164
  • LY300164

Pharmacology

Indication

For the treatment of epilepsy.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Talampanel, 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 action

Talampanel 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.

TargetActionsOrganism
UGlutamate receptor 1Not AvailableHumans
UGlutamate receptor 2Not AvailableHumans
UGlutamate receptor 3Not AvailableHumans
UGlutamate receptor 4Not AvailableHumans
Absorption

Rapidly absorbed, with maximal plasma concentrations achieved within 1-3 hours.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

3-6 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
Not Available
Direct Parent
Benzodiazepines
Alternative Parents
Benzodioxoles / Aniline and substituted anilines / Acetamides / Amino acids and derivatives / Oxacyclic compounds / Azacyclic compounds / Acetals / Primary amines / Organopnictogen compounds / Organic oxides
show 2 more
Substituents
Acetal / Acetamide / Amine / Amino acid or derivatives / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzodiazepine / Benzodioxole
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzodioxoles (CHEBI:34992)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
CVS43XG1L5
CAS number
161832-65-1
InChI Key
JACAAXNEHGBPOQ-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[7.5.0.0^{3,7}]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

References

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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
KEGG Drug
D02696
KEGG Compound
C13670
PubChem Compound
164509
PubChem Substance
175426925
ChemSpider
144217
BindingDB
50173337
ChEBI
34992
ChEMBL
CHEMBL61872
ZINC
ZINC000003823565
Wikipedia
Talampanel

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2CompletedTreatmentCentral Nervous System Neoplasm1
2CompletedTreatmentDyskinesia / Parkinson's Disease (PD)1
2CompletedTreatmentEpilepsies1
2CompletedTreatmentGlioblastoma Multiforme (GBM)1
2CompletedTreatmentHealthy Subjects (HS)1
2CompletedTreatmentParkinson's Disease (PD)1
2TerminatedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2TerminatedTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Oligodendroglioma (AO) / Glioblastoma Multiforme (GBM) / Mixed Anaplastic Oligoastrocytoma (AOA)1
1CompletedTreatmentHealthy Subjects (HS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not 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 RuleNoChemaxon
MDDR-like RuleNoChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

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Details1. Glutamate receptor 1
Kind
Protein
Organism
Humans
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 co...
Gene Name
GRIA1
Uniprot ID
P42261
Uniprot Name
Glutamate receptor 1
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. [Article]
  2. Howes JF, Bell C: Talampanel. Neurotherapeutics. 2007 Jan;4(1):126-9. [Article]
  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. [Article]
Details2. Glutamate receptor 2
Kind
Protein
Organism
Humans
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 ne...
Gene Name
GRIA2
Uniprot ID
P42262
Uniprot Name
Glutamate receptor 2
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. [Article]
  2. Howes JF, Bell C: Talampanel. Neurotherapeutics. 2007 Jan;4(1):126-9. [Article]
  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. [Article]
Details3. Glutamate receptor 3
Kind
Protein
Organism
Humans
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 ne...
Gene Name
GRIA3
Uniprot ID
P42263
Uniprot Name
Glutamate receptor 3
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. [Article]
  2. Howes JF, Bell C: Talampanel. Neurotherapeutics. 2007 Jan;4(1):126-9. [Article]
  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. [Article]
Details4. Glutamate receptor 4
Kind
Protein
Organism
Humans
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 ne...
Gene Name
GRIA4
Uniprot ID
P48058
Uniprot Name
Glutamate receptor 4
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. [Article]
  2. Howes JF, Bell C: Talampanel. Neurotherapeutics. 2007 Jan;4(1):126-9. [Article]
  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. [Article]

Drug created at October 21, 2007 22:23 / Updated at January 14, 2023 19:03