Talaglumetad

Last updated

Talaglumetad
LY544344 structure.png
Clinical data
Other namesLY-544344; LY544344
Drug class Metabotropic glutamate mGlu2 and mGlu3 receptor agonist
ATC code
  • None
Pharmacokinetic data
Bioavailability 85% [1]
Identifiers
  • (1S,2S,5R,6S)-2-[[(2S)-2-aminopropanoyl]amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C11H16N2O5
Molar mass 256.258 g·mol−1
3D model (JSmol)
  • C[C@@H](C(=O)N[C@]1(CC[C@@H]2[C@H]1[C@H]2C(=O)O)C(=O)O)N
  • InChI=1S/C11H16N2O5/c1-4(12)8(14)13-11(10(17)18)3-2-5-6(7(5)11)9(15)16/h4-7H,2-3,12H2,1H3,(H,13,14)(H,15,16)(H,17,18)/t4-,5-,6-,7-,11-/m0/s1
  • Key:UPSXYNJDCKOCFD-QIMCWZKGSA-N

Talaglumetad (INN Tooltip International Nonproprietary Name, USAN Tooltip United States Adopted Name; developmental code name LY-544344) is a metabotropic glutamate mGlu2 and mGlu3 receptor agonist which was under development for the treatment of generalized anxiety disorder. [2]

Contents

Pharmacology

The drug is a prodrug of eglumetad (LY-354740), a potent and selective metabotropic glutamate mGlu2 and mGlu3 receptor agonist. [3] [4] [1] Eglumetad showed modest oral bioavailability (~10%) and brain penetration in animal and human studies, so talaglumetad was developed to enhance its pharmacokinetic properties for clinical use. [4] [1] Through uptake by the peptide transporter 1 (PepT1), the drug increased systemic exposure to eglumetad in humans by approximately 13-fold relative to administration of eglumetad itself, with an approximate oral bioavailability of 85%. [5] [1] Eglumetad shows anxiolytic-like effects in animals and talaglumetad produced anxiolytic effects in humans. [4] The drug did not produce the problematic side effects typical of benzodiazepines in clinical studies. [4]

Development

Talaglumetad was under development by Eli Lilly and Company. [2] It appears to have been under development until at least 2005. [3] The drug reached phase 2 clinical trials for treatment of generalized anxiety disorder. [4] However, development of talaglumetad was discontinued due to findings of convulsions in preclinical rodent studies. [4]

See also

References

  1. 1 2 3 4 Vig BS, Huttunen KM, Laine K, Rautio J (October 2013). "Amino acids as promoieties in prodrug design and development". Advanced Drug Delivery Reviews. 65 (10): 1370–1385. doi:10.1016/j.addr.2012.10.001. PMID   23099277.
  2. 1 2 "Talaglumetad". AdisInsight. 31 March 2009. Retrieved 1 October 2025.
  3. 1 2 Danysz W (September 2005). "LY-544344. Eli Lilly". IDrugs. 8 (9): 755–762. PMID   16118698.
  4. 1 2 3 4 5 6 Spooren W, Lesage A, Lavreysen H, Gasparini F, Steckler T (2010). "Metabotropic glutamate receptors: their therapeutic potential in anxiety". Behavioral Neurobiology of Anxiety and Its Treatment. Curr Top Behav Neurosci. Vol. 2. pp. 391–413. doi:10.1007/7854_2010_36. ISBN   978-3-642-02911-0. PMID   21309118.
  5. ↑ Vig B, Rautio J (August 2011). "Amino acid prodrugs for oral delivery: challenges and opportunities". Therapeutic Delivery. 2 (8): 959–962. doi:10.4155/tde.11.75. PMID   22826863.
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