Talampanel | LY300164 | CAS#161832-65-1 | Glutamate Receptor Inhibitor

MedKoo Cat#: 202740 | Name: Talampanel

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Talampanel, also known as LY300164 and GYKI-53773, is a glutamate receptor inhibitor with anti-seizure activity. Talampanel is also an orally active, potent and selective AMPA-receptor antagonist, and can noncompetitively bind to the AMPA subtype of glutamate excitatory amino acid receptors and may inhibit the growth of gliomas by interfering with neurotransmitters involved in brain tumor growth. This agent may also protect against traumatic brain injury. Talampanel (GYKI 53405) is being investigated for the treatment of epilepsy, malignant gliomas and amyotrophic lateral sclerosis (ALS). As of May 2010, results from the trial for ALS have been found negative.

Chemical Structure

Talampanel

CAS#161832-65-1

Theoretical Analysis

MedKoo Cat#: 202740

Name: Talampanel

CAS#: 161832-65-1

Chemical Formula: C19H19N3O3

Exact Mass: 337.1426

Molecular Weight: 337.37

Elemental Analysis: C, 67.64; H, 5.68; N, 12.46; O, 14.23

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,850.00	Ready to ship
1g	USD 4,250.00	Ready to ship
2g	USD 7,250.00	Ready to ship

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Synonym

LY300164, LY 300164, LY-300164, GYKI53773, Gyki 53405, Gyki-53405, LY293606, LY-293606, LY 293606, Talampanel

IUPAC/Chemical Name

(8R)-7-Acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3]benzodiazepine

InChi Key

JACAAXNEHGBPOQ-LLVKDONJSA-N

InChi Code

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

SMILES Code

C[C@H]1N(C(C)=O)N=C(C2=CC=C(N)C=C2)C3=CC(OCO4)=C4C=C3C1

Appearance

White solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Talampanel is currently being investigated for the treatment of epilepsy, malignant gliomas and amyotrophic lateral sclerosis (ALS). It is a noncompetitive antagonist of the AMPA receptor, a type of glutamate receptor in the central nervous system. (source: http://en.wikipedia.org/wiki/Talampanel). Teva has exclusive worldwide rights to develop and market talampanel for the treatment of neurological disorders. Based on talampanel',s anti-glutamate excitatory activity, Teva believes that talampanel can significantly delay the functional deterioration of ALS patients. Based on the scientific, mechanistic rationale and a positive signal from a small Phase II study in ALS, Teva is proceeding with the development of talampanel for the latter indication, and a Phase II study has been initiated in centers in the U.S., Canada, Europe, and Israel. to evaluate the efficacy, tolerability and safety of an oral administration of 75mg and 150mg daily doses of talampanel for 52 weeks.The recruitment of 559 ALS patients has been completed and the study is scheduled to end by the second quarter of 2010. (source: http://www.tevapharm.com/research/products_ni.asp#Talampanel). On May 17, 2010, Teva announced the results of the recently completed trial of Talampanel for people with ALS. The results were conclusively negative. The ALS Functional Rating scale, a tool instrument used to assess changes in physical functioning in people with ALS over time, was the primary outcome measure; both this measure and the other measures investigated showed no difference in the rate of progression in participants with ALS treated with placebo or either of 2 doses of the study medication. While there were more side effects seen in participants treated with the Talampanel, the dropout rates were very similar in all groups, making the negative results more convincing. While this is a very disappointing result for patients, caregivers, and physicians, the convincing nature of the results provides a clear answer to the effectiveness of this treatment for people with ALS. Fortunately, there are many other promising drugs now being tested; it is important for all to remain hopeful and committed to finding improved therapies for ALS. (sourcing: http://www.alsa.org/patient/drug.cfm?id=1370).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#KB200723

QC Data

View QC data: current batch, Lot#KB200723

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Talampanel (LY300164) is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist.

In vitro activity:

The mechanism of action of BDZ-d (talampanel) on the GluA2 AMPA receptor was investigated. Shown in Figure 4a are representative whole-cell current traces obtained from the laser-pulse photolysis measurement. As a control (upper trace in Figure 4a), the rise of the glutamate-evoked whole-cell current reflected the opening of the GluA2 channels from a single HEK-293 cell. In the presence of BDZ-d (lower trace), the rate of the current rise on the same cell was slowed and the amplitude of the whole-cell current was reduced. Furthermore, that the channel-opening rate remained single exponential at any concentration of glutamate (i.e., between 100 ± 20 μM and 300 ± 50 μM) with and without inhibitor (for up to 60 μM) was consistent with the assumption that the binding of the inhibitor/glutamate was fast relative to the channel opening. These results suggested that BDZ-d inhibited the GluA2 channel-opening rate, rather than the rate process of ligand binding. Reference: ACS Chem Neurosci. 2013 Apr 17;4(4):635-44. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629739/

In vivo activity:

The efficacy of talampanel (GYKI 53773) was tested in a rodent model of hypoxic neonatal seizures.Acute hypoxia-induced seizures were suppressed by talampanel in a dose-related manner within the range of administration from 1–10 mg/kg. Vehicle-treated rats responded initially to hypoxia with myoclonic jerks, followed by the onset of tonic–clonic head and trunk movement. To determine treatment efficacy, the number of episodes of tonic–clonic seizures were compared between groups. Compared to vehicle-treated animals, the anticonvulsant activity of talampanel was maximal at 7.5 and 10 mg/kg, where seizures were blocked 74.6% at 10 mg/kg (25.4 ± 7.3, n = 17; p < 0.001) and 86.7% at 7.5 mg/kg (13.4 ± 3.2, n = 17; p < 0.001) (Fig. 1). The effect on time spent in tonic–clonic seizure activity was less at the lower doses of 1 mg/kg (52.6 ± 11.3, n = 7; p = 0.056) and 5 mg/kg (44.28 ± 10.4, n = 17; p = 0.002). Overall, talampanel treatment suppressed seizures in a dose-dependent manner. Reference: Epilepsia. 2009 Apr;50(4):694-701. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672962/

	Solvent	mg/mL	mM
Solubility
	DMSO	47.9	142.01
	DMF	30.0	88.92
	DMF:PBS (pH 7.2) (1:5)	0.2	0.47

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 337.37 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Wang C, Niu L. Mechanism of inhibition of the GluA2 AMPA receptor channel opening by talampanel and its enantiomer: the stereochemistry of the 4-methyl group on the diazepine ring of 2,3-benzodiazepine derivatives. ACS Chem Neurosci. 2013 Apr 17;4(4):635-44. doi: 10.1021/cn3002398. Epub 2013 Feb 12. PMID: 23402301; PMCID: PMC3629739. 2. Aujla PK, Fetell MR, Jensen FE. Talampanel suppresses the acute and chronic effects of seizures in a rodent neonatal seizure model. Epilepsia. 2009 Apr;50(4):694-701. doi: 10.1111/j.1528-1167.2008.01947.x. Epub 2009 Feb 12. PMID: 19220413; PMCID: PMC2672962. 3. 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. doi: 10.1089/08977150152693728. PMID: 11686490.

In vitro protocol:

In vivo protocol:

1. Aujla PK, Fetell MR, Jensen FE. Talampanel suppresses the acute and chronic effects of seizures in a rodent neonatal seizure model. Epilepsia. 2009 Apr;50(4):694-701. doi: 10.1111/j.1528-1167.2008.01947.x. Epub 2009 Feb 12. PMID: 19220413; PMCID: PMC2672962. 2. 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. doi: 10.1089/08977150152693728. PMID: 11686490.

1: Masumoto N, Kato S, Aichi M, Hasegawa S, Sahara K, Suyama K, Sano A, Miyazaki T, Okudela K, Kaneko T, Takahashi T. AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell lines. Thorac Cancer. 2023 Oct;14(29):2897-2908. doi: 10.1111/1759-7714.15075. Epub 2023 Aug 22. PMID: 37605807; PMCID: PMC10569908. 2: Charsouei S, Jabalameli MR, Karimi-Moghadam A. Molecular insights into the role of AMPA receptors in the synaptic plasticity, pathogenesis and treatment of epilepsy: therapeutic potentials of perampanel and antisense oligonucleotide (ASO) technology. Acta Neurol Belg. 2020 Jun;120(3):531-544. doi: 10.1007/s13760-020-01318-1. Epub 2020 Mar 9. PMID: 32152997. 3: Inami H, Shishikura JI, Yasunaga T, Hirano M, Kimura T, Yamashita H, Ohno K, Sakamoto S. Synthesis and Pharmacological Evaluation of 3-[(4-Oxo-4H-pyrido[3,2-e][1,3]thiazin-2-yl)(phenyl)amino]propanenitrile Derivatives as Orally Active AMPA Receptor Antagonists. Chem Pharm Bull (Tokyo). 2019;67(7):699-706. doi: 10.1248/cpb.c18-00977. PMID: 31257325. 4: Valko K, Ciesla L. Amyotrophic lateral sclerosis. Prog Med Chem. 2019;58:63-117. doi: 10.1016/bs.pmch.2018.12.001. Epub 2019 Mar 8. PMID: 30879475. 5: Haq SF, Shanbhag AP, Karthikeyan S, Hassan I, Thanukrishnan K, Ashok A, Sukumaran S, Ramaswamy S, Bharatham N, Datta S, Samant S, Katagihallimath N. A strategy to identify a ketoreductase that preferentially synthesizes pharmaceutically relevant (S)-alcohols using whole-cell biotransformation. Microb Cell Fact. 2018 Dec 3;17(1):192. doi: 10.1186/s12934-018-1036-2. PMID: 30509260; PMCID: PMC6276252. 6: Patai R, Paizs M, Tortarolo M, Bendotti C, Obál I, Engelhardt JI, Siklós L. Presymptomatically applied AMPA receptor antagonist prevents calcium increase in vulnerable type of motor axon terminals of mice modeling amyotrophic lateral sclerosis. Biochim Biophys Acta Mol Basis Dis. 2017 Jul;1863(7):1739-1748. doi: 10.1016/j.bbadis.2017.05.016. Epub 2017 May 17. PMID: 28528135. 7: Yoo SW, Bae M, Tovar-Y-Romo LB, Haughey NJ. Hippocampal encoding of interoceptive context during fear conditioning. Transl Psychiatry. 2017 Jan 3;7(1):e991. doi: 10.1038/tp.2016.254. PMID: 28045462; PMCID: PMC5545722. 8: Griffin DE. Alphavirus Encephalomyelitis: Mechanisms and Approaches to Prevention of Neuronal Damage. Neurotherapeutics. 2016 Jul;13(3):455-60. doi: 10.1007/s13311-016-0434-6. PMID: 27114366; PMCID: PMC4965404. 9: Dhir A, Chavda V. Pre- and post-exposure talampanel (GYKI 53773) against kainic acid seizures in neonatal rats. Pharmacol Rep. 2016 Feb;68(1):190-5. doi: 10.1016/j.pharep.2015.08.011. Epub 2015 Sep 1. PMID: 26721372. 10: Okonogi N, Shirai K, Oike T, Murata K, Noda SE, Suzuki Y, Nakano T. Topics in chemotherapy, molecular-targeted therapy, and immunotherapy for newly- diagnosed glioblastoma multiforme. Anticancer Res. 2015 Mar;35(3):1229-35. PMID: 25750269. 11: Matsumura N, Nakaki T. Isobolographic analysis of the mechanisms of action of anticonvulsants from a combination effect. Eur J Pharmacol. 2014 Oct 15;741:237-46. doi: 10.1016/j.ejphar.2014.08.001. Epub 2014 Aug 19. PMID: 25149665. 12: Yacila G, Sari Y. Potential therapeutic drugs and methods for the treatment of amyotrophic lateral sclerosis. Curr Med Chem. 2014;21(31):3583-93. doi: 10.2174/0929867321666140601162710. PMID: 24934355; PMCID: PMC4182116. 13: Blecic S, Rynkowski M, De Witte O, Lefranc F. Glutamate et gliomes malins, de l'épilepsie à l'agressivité biologique : implications thérapeutiques [Glutamate and malignant gliomas, from epilepsia to biological aggressiveness: therapeutic implications]. Bull Cancer. 2013 Sep;100(9):829-35. French. doi: 10.1684/bdc.2013.1781. PMID: 23883552. 14: Zaccara G, Giovannelli F, Cincotta M, Iudice A. AMPA receptor inhibitors for the treatment of epilepsy: the role of perampanel. Expert Rev Neurother. 2013 Jun;13(6):647-55. doi: 10.1586/ern.13.46. PMID: 23739002. 15: Wang C, Niu L. Mechanism of inhibition of the GluA2 AMPA receptor channel opening by talampanel and its enantiomer: the stereochemistry of the 4-methyl group on the diazepine ring of 2,3-benzodiazepine derivatives. ACS Chem Neurosci. 2013 Apr 17;4(4):635-44. doi: 10.1021/cn3002398. Epub 2013 Feb 12. PMID: 23402301; PMCID: PMC3629739. 16: Paizs M, Tortarolo M, Bendotti C, Engelhardt JI, Siklós L. Talampanel reduces the level of motoneuronal calcium in transgenic mutant SOD1 mice only if applied presymptomatically. Amyotroph Lateral Scler. 2011 Sep;12(5):340-4. doi: 10.3109/17482968.2011.584627. Epub 2011 May 30. PMID: 21623665; PMCID: PMC3231880. 17: Arribas Alpuente L, Menéndez López A, Yayá Tur R. Glioblastoma: changing expectations? Clin Transl Oncol. 2011 Apr;13(4):240-8. doi: 10.1007/s12094-011-0648-3. PMID: 21493184. 18: de Groot J, Sontheimer H. Glutamate and the biology of gliomas. Glia. 2011 Aug;59(8):1181-9. doi: 10.1002/glia.21113. Epub 2010 Dec 29. PMID: 21192095; PMCID: PMC3107875. 19: Siciliano G, Carlesi C, Pasquali L, Piazza S, Pietracupa S, Fornai F, Ruggieri S, Murri L. Clinical trials for neuroprotection in ALS. CNS Neurol Disord Drug Targets. 2010 Jul;9(3):305-13. doi: 10.2174/187152710791292648. PMID: 20406180. 20: Grossman SA, Ye X, Piantadosi S, Desideri S, Nabors LB, Rosenfeld M, Fisher J; NABTT CNS Consortium. Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res. 2010 Apr 15;16(8):2443-9. doi: 10.1158/1078-0432.CCR-09-3106. Epub 2010 Apr 6. PMID: 20371685; PMCID: PMC2861898.