Chemistry:Talaglumetad
Talaglumetad (INN, USAN; 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.[1]
Pharmacology
The drug is a prodrug of eglumetad (LY-354740), a potent and selective metabotropic glutamate mGlu2 and mGlu3 receptor agonist.[2][3][4] 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.[3][4] 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][4] Eglumetad shows anxiolytic-like effects in animals and talaglumetad produced anxiolytic effects in humans.[3] The drug did not produce the problematic side effects typical of benzodiazepines in clinical studies.[3]
Development
Talaglumetad was under development by Eli Lilly and Company.[1] It appears to have been under development until at least 2005.[2] The drug reached phase 2 clinical trials for treatment of generalized anxiety disorder.[3] However, development of talaglumetad was discontinued due to findings of convulsions in preclinical rodent studies.[3]
See also
- Eglumetad
- Pomaglumetad
- Pomaglumetad methionil
References
- ↑ 1.0 1.1 "Talaglumetad". 31 March 2009. https://adisinsight.springer.com/drugs/800018821.
- ↑ 2.0 2.1 "LY-544344. Eli Lilly". IDrugs 8 (9): 755–762. September 2005. PMID 16118698.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 "Metabotropic glutamate receptors: their therapeutic potential in anxiety". Behavioral Neurobiology of Anxiety and Its Treatment. Curr Top Behav Neurosci. 2. 2010. pp. 391–413. doi:10.1007/7854_2010_36. ISBN 978-3-642-02911-0.
- ↑ 4.0 4.1 4.2 "Amino acids as promoieties in prodrug design and development". Advanced Drug Delivery Reviews 65 (10): 1370–1385. October 2013. doi:10.1016/j.addr.2012.10.001. PMID 23099277.
- ↑ "Amino acid prodrugs for oral delivery: challenges and opportunities". Therapeutic Delivery 2 (8): 959–962. August 2011. doi:10.4155/tde.11.75. PMID 22826863.
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