Talaglumetad

Talaglumetad (INNTooltip International Nonproprietary Name, USANTooltip 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]

Talaglumetad

Clinical data
Other names	LY-544344; LY544344
Drug class	Metabotropic glutamate mGlu2 and mGlu3 receptor agonist
ATC code	None
Pharmacokinetic data
Bioavailability	85%[1]
Identifiers
IUPAC name (1S,2S,5R,6S)-2-{{#parsoidfragment:2}}(2S)-2-aminopropanoyl]amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid
CAS Number	441765-98-6
PubChem CID	9857256
DrugBank	DB19742
ChemSpider	8032956
UNII	2OXQ1Z504M
ChEMBL	ChEMBL1189257
CompTox Dashboard (EPA)	DTXSID801351482
Chemical and physical data
Formula	C11H16N2O5
Molar mass	256.258 g·mol−1
3D model (JSmol)	Interactive image
SMILES 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 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

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

• Eglumetad
• Pomaglumetad
• Pomaglumetad methionil