Talampanel

Talampanel (INN; development codes GYKI 537773 and LY300164) is a drug which has been investigated for the treatment of epilepsy,[1][2] malignant gliomas,[3] and amyotrophic lateral sclerosis (ALS).[4]

Talampanel

Clinical data
ATC code	none
Legal status
Legal status	Investigational
Identifiers
IUPAC name (8R)-7-Acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3]benzodiazepine
CAS Number	161832-65-1^N
PubChem CID	164509
ChemSpider	144217^N
UNII	CVS43XG1L5
ChEMBL	ChEMBL61872^N
CompTox Dashboard (EPA)	DTXSID10167259
ECHA InfoCard	100.230.001
Chemical and physical data
Formula	C19H19N3O3
Molar mass	337.379 g·mol^−1
3D model (JSmol)	Interactive image
SMILES Nc4ccc(cc4)C(=NN2C(=O)C)c3cc1OCOc1cc3CC2C
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^N Key:JACAAXNEHGBPOQ-LLVKDONJSA-N^N
^NY (what is this?)  (verify)

As of May 2010, results from the trial for ALS have been found negative.[5] Talampanel is not currently under development.

Talampanel acts as a non-competitive antagonist of the AMPA receptor, a type of ionotropic glutamate receptor in the central nervous system.[6]

It showed effectiveness for epilepsy in clinical trials but its development was suspended due to its poor pharmacokinetic profile, namely a short terminal half-life (3 hours) that necessitated multiple doses per day.[7]

References

1. Luszczki, J. J. (2009). "Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions". Pharmacological reports : PR. 61 (2): 197–216. doi:10.1016/s1734-1140(09)70024-6. PMID 19443931.
2. Bialer, M.; Johannessen, S. I.; Kupferberg, H. J.; Levy, R. H.; Perucca, E.; Tomson, T. R. (2007). "Progress report on new antiepileptic drugs: A summary of the Eighth Eilat Conference (EILAT VIII)". Epilepsy Research. 73 (1): 1–52. doi:10.1016/j.eplepsyres.2006.10.008. PMID 17158031.
3. Iwamoto, F. M.; Kreisl, T. N.; Kim, L.; Duic, J. P.; Butman, J. A.; Albert, P. S.; Fine, H. A. (2010). "Phase II Trial of Talampanel, a Glutamate Receptor Inhibitor, for Adults with Recurrent Malignant Gliomas". Cancer. 116 (7): 1776–1782. doi:10.1002/cncr.24957. PMC 2846997. PMID 20143438.
4. Pascuzzi, R. M.; Shefner, J.; Chappell, A. S.; Bjerke, J. S.; Tamura, R.; Chaudhry, V.; Clawson, L.; Haas, L.; Rothstein, J. D. (2009). "A phase II trial of talampanel in subjects with amyotrophic lateral sclerosis". Amyotrophic Lateral Sclerosis. 11 (3): 266–271. doi:10.3109/17482960903307805. PMID 19961264.
5. Talampanel Trial, Talampanel Trial on alsa.org
6. Aujla, P. K.; Fetell, M. R.; Jensen, F. E. (2009). "Talampanel suppresses the acute and chronic effects of seizures in a rodent neonatal seizure model". Epilepsia. 50 (4): 694–701. doi:10.1111/j.1528-1167.2008.01947.x. PMC 2672962. PMID 19220413.
7. Lee K, Goodman L, Fourie C, Schenk S, Leitch B, Montgomery JM (2016). "AMPA Receptors as Therapeutic Targets for Neurological Disorders". Adv Protein Chem Struct Biol. Advances in Protein Chemistry and Structural Biology. 103: 203–61. doi:10.1016/bs.apcsb.2015.10.004. ISBN 9780128047941. PMID 26920691.