Talampanel

Identification

Name
Talampanel
Accession Number
DB04982
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
GYKI-53773 / LY-300164 / LY300164
International/Other Brands
Ampanel / Kinampa
Categories
UNII
CVS43XG1L5
CAS number
161832-65-1
Weight
Average: 337.3725
Monoisotopic: 337.142641489
Chemical Formula
C19H19N3O3
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[7.5.0.0³,⁷]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

Indication

For the treatment of epilepsy.

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 AvailableHuman
UGlutamate receptor 2Not AvailableHuman
UGlutamate receptor 3Not AvailableHuman
UGlutamate receptor 4Not AvailableHuman
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

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

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
1, 2CompletedTreatmentDyskinesias / Movement Disorders / Parkinson's Disease (PD)1
2CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2CompletedTreatmentBrain and Central Nervous System Tumors1
2CompletedTreatmentDyskinesias / Parkinson's Disease (PD)1
2CompletedTreatmentEpilepsies1
2CompletedTreatmentGlioblastoma Multiforme (GBM)1
2CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentParkinson's Disease (PD)1
2TerminatedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2TerminatedTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Mixed Oligoastrocytoma / Anaplastic Oligodendroglioma (AO) / Glioblastoma Multiforme (GBM)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

Taxonomy

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
Benzodiazepine / Benzodioxole / Aniline or substituted anilines / Monocyclic benzene moiety / Benzenoid / Acetamide / Amino acid or derivatives / Acetal / Carboxylic acid derivative / Oxacycle
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzodioxoles (CHEBI:34992)

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 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. [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 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. [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 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. [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 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. [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]

Drug created on October 21, 2007 16:23 / Updated on August 02, 2018 05:28