Talampanel
Explore a selection of our essential drug information below, or:
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
- 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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- 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.
Target Actions Organism UGlutamate receptor 1 Not Available Humans UGlutamate receptor 2 Not Available Humans UGlutamate receptor 3 Not Available Humans UGlutamate receptor 4 Not Available Humans - 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- External Links
- 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
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data2 Completed Treatment Amyotrophic Lateral Sclerosis (ALS) 1 somestatus stop reason just information to hide 2 Completed Treatment Brain and Central Nervous System Tumors 1 somestatus stop reason just information to hide 2 Completed Treatment Dyskinesia / Parkinson's Disease (PD) 1 somestatus stop reason just information to hide 2 Completed Treatment Epilepsy 1 somestatus stop reason just information to hide 2 Completed Treatment Glioblastoma Multiforme (GBM) 1 somestatus stop reason just information to hide
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
Property Value Source Water Solubility 0.126 mg/mL ALOGPS logP 1.97 ALOGPS logP 2.33 Chemaxon logS -3.4 ALOGPS pKa (Strongest Basic) 3.38 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 77.15 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 94.65 m3·mol-1 Chemaxon Polarizability 36.34 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9604 Caco-2 permeable + 0.5108 P-glycoprotein substrate Non-substrate 0.6808 P-glycoprotein inhibitor I Non-inhibitor 0.6984 P-glycoprotein inhibitor II Inhibitor 0.6921 Renal organic cation transporter Non-inhibitor 0.8149 CYP450 2C9 substrate Non-substrate 0.8327 CYP450 2D6 substrate Non-substrate 0.8135 CYP450 3A4 substrate Substrate 0.7208 CYP450 1A2 substrate Inhibitor 0.7402 CYP450 2C9 inhibitor Inhibitor 0.7333 CYP450 2D6 inhibitor Non-inhibitor 0.7342 CYP450 2C19 inhibitor Inhibitor 0.7168 CYP450 3A4 inhibitor Inhibitor 0.589 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9152 Ames test Non AMES toxic 0.5 Carcinogenicity Non-carcinogens 0.6491 Biodegradation Not ready biodegradable 0.9881 Rat acute toxicity 2.7049 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9984 hERG inhibition (predictor II) Non-inhibitor 0.8278
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0029000000-6ab36c34d180d5cc527f Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0009000000-cb79103c3cf875ef1e72 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0049000000-698f109b74c65ce12ba9 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-000l-0079000000-92f6e7f5ac4978d943ac Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-016r-2192000000-ac60e98fa5444946052f Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-2209000000-6f4b0fe979bba47d12a3 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 192.8389617 predictedDarkChem Lite v0.1.0 [M-H]- 174.3607 predictedDeepCCS 1.0 (2019) [M+H]+ 194.1306617 predictedDarkChem Lite v0.1.0 [M+H]+ 176.7187 predictedDeepCCS 1.0 (2019) [M+Na]+ 193.1986617 predictedDarkChem Lite v0.1.0 [M+Na]+ 183.4256 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (PubMed:1311100, PubMed:20805473, PubMed:21172611, PubMed:28628100, PubMed:35675825). 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 upon entry of monovalent and divalent cations such as sodium and calcium. The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist (By similarity). In the presence of CACNG2 or CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate (PubMed:21172611). Resensitization is blocked by CNIH2 through interaction with CACNG8 in the CACNG8-containing AMPA receptors complex (PubMed:21172611). Calcium (Ca(2+)) permeability depends on subunits composition and, heteromeric channels containing edited GRIA2 subunit are calcium-impermeable. Also permeable to other divalents cations such as strontium(2+) and magnesium(2+) and monovalent cations such as potassium(1+) and lithium(1+) (By similarity)
- Specific Function
- adenylate cyclase binding
- Gene Name
- GRIA1
- Uniprot ID
- P42261
- Uniprot Name
- Glutamate receptor 1
- Molecular Weight
- 101505.245 Da
References
- 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]
- Howes JF, Bell C: Talampanel. Neurotherapeutics. 2007 Jan;4(1):126-9. [Article]
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (PubMed:20614889, PubMed:31300657, PubMed:8003671). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system and plays an important role in fast excitatory synaptic transmission (PubMed:14687553). 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 upon entry of monovalent and divalent cations such as sodium and calcium (PubMed:20614889, PubMed:8003671). The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist (By similarity). In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate (By similarity). Through complex formation with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity)
- Specific Function
- AMPA glutamate receptor activity
- Gene Name
- GRIA2
- Uniprot ID
- P42262
- Uniprot Name
- Glutamate receptor 2
- Molecular Weight
- 98820.32 Da
References
- 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]
- Howes JF, Bell C: Talampanel. Neurotherapeutics. 2007 Jan;4(1):126-9. [Article]
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (By similarity). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system and plays an important role in fast excitatory synaptic transmission by inducing long-term potentiation (By similarity). 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 upon entry of calcium (PubMed:17989220). The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist (PubMed:17989220). In the presence of CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate (PubMed:21172611)
- Specific Function
- AMPA glutamate receptor activity
- Gene Name
- GRIA3
- Uniprot ID
- P42263
- Uniprot Name
- Glutamate receptor 3
- Molecular Weight
- 101155.975 Da
References
- 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]
- Howes JF, Bell C: Talampanel. Neurotherapeutics. 2007 Jan;4(1):126-9. [Article]
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (By similarity). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system and plays an important role in fast excitatory synaptic transmission (By similarity). 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 upon entry of monovalent and divalent cations such as sodium and calcium. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist (By similarity). In the presence of CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate (PubMed:21172611)
- Specific Function
- AMPA glutamate receptor activity
- Gene Name
- GRIA4
- Uniprot ID
- P48058
- Uniprot Name
- Glutamate receptor 4
- Molecular Weight
- 100870.085 Da
References
- 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]
- Howes JF, Bell C: Talampanel. Neurotherapeutics. 2007 Jan;4(1):126-9. [Article]
- 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