Talampanel

{{Short description|Chemical compound}}

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{{Drugbox

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

| image = Talampanel skeletal.svg

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| legal_status = Investigational

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| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 161832-65-1

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| PubChem = 164509

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| UNII = CVS43XG1L5

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| ChEMBL = 61872

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| chemical_formula =

| C=19 | H=19 | N=3 | O=3

| smiles = Nc4ccc(cc4)C(=NN2C(=O)C)c3cc1OCOc1cc3CC2C

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| StdInChI = 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

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Talampanel (INN; development codes GYKI 537773 and LY300164) is a drug which has been investigated for the treatment of epilepsy,{{cite journal | vauthors = Luszczki JJ | title = Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions | journal = Pharmacological Reports | volume = 61 | issue = 2 | pages = 197–216 | year = 2009 | pmid = 19443931 | doi = 10.1016/s1734-1140(09)70024-6 | s2cid = 72918370 }}{{cite journal | vauthors = Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Perucca E, Tomson T | title = Progress report on new antiepileptic drugs: a summary of the {{sic|Eigth}} Eilat Conference (EILAT VIII) | journal = Epilepsy Research | volume = 73 | issue = 1 | pages = 1–52 | date = January 2007 | pmid = 17158031 | doi = 10.1016/j.eplepsyres.2006.10.008 | s2cid = 45026113 }} malignant gliomas,{{cite journal | vauthors = Iwamoto FM, Kreisl TN, Kim L, Duic JP, Butman JA, Albert PS, Fine HA | title = Phase 2 trial of talampanel, a glutamate receptor inhibitor, for adults with recurrent malignant gliomas | journal = Cancer | volume = 116 | issue = 7 | pages = 1776–1782 | date = April 2010 | pmid = 20143438 | pmc = 2846997 | doi = 10.1002/cncr.24957 }} and amyotrophic lateral sclerosis (ALS).{{cite journal | vauthors = Pascuzzi RM, Shefner J, Chappell AS, Bjerke JS, Tamura R, Chaudhry V, Clawson L, Haas L, Rothstein JD | display-authors = 6 | title = A phase II trial of talampanel in subjects with amyotrophic lateral sclerosis | journal = Amyotrophic Lateral Sclerosis | volume = 11 | issue = 3 | pages = 266–271 | date = May 2010 | pmid = 19961264 | doi = 10.3109/17482960903307805 | s2cid = 7388452 }}

As of May 2010, results from the trial for ALS have been found negative.{{cite web | url = http://www.alsa.org/research/clinical-trials/talampanel-trial.html | title = Talampanel Trial | archive-url = https://web.archive.org/web/20110323031100/http://www.alsa.org/research/clinical-trials/talampanel-trial.html | archive-date= 2011-03-23 | url-status = dead | work = alsa.org | date = May 2010 }} 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.{{cite journal | vauthors = Aujla PK, Fetell MR, Jensen FE | title = Talampanel suppresses the acute and chronic effects of seizures in a rodent neonatal seizure model | journal = Epilepsia | volume = 50 | issue = 4 | pages = 694–701 | date = April 2009 | pmid = 19220413 | pmc = 2672962 | doi = 10.1111/j.1528-1167.2008.01947.x }}

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.{{cite book | vauthors = Lee K, Goodman L, Fourie C, Schenk S, Leitch B, Montgomery JM | title = Ion Channels as Therapeutic Targets, Part A | chapter = AMPA Receptors as Therapeutic Targets for Neurological Disorders | volume = 103 | pages = 203–261 | year = 2016 | pmid = 26920691 | doi = 10.1016/bs.apcsb.2015.10.004 | isbn = 9780128047941 | series = Advances in Protein Chemistry and Structural Biology }}