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Traneurocin

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Traneurocin
Clinical data
Other namesCycloprolylglycine; Cyclo-Gly-Pro; Cyclo-Pro-Gly; CGP; Cyclo-GP; Biocovax; Biomedivir; Dexaneurosone; NA-831; NA-81; Nanomedivir; Neurosivir; Traneurocine; (S)-Hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
Drug classNeuroprotective; Neurogenesis stimulant; Cognitive enhancer
Pharmacokinetic data
Elimination half-life7 hours[1]
Identifiers
  • (8aS)-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC7H10N2O2
Molar mass154.169 g·mol−1
3D model (JSmol)
  • C1C[C@H]2C(=O)NCC(=O)N2C1
  • InChI=1S/C7H10N2O2/c10-6-4-8-7(11)5-2-1-3-9(5)6/h5H,1-4H2,(H,8,11)/t5-/m0/s1
  • Key:OWOHLURDBZHNGG-YFKPBYRVSA-N

Traneurocin (developmental code name NA-831), also known as cycloprolylglycine (CPG), is a racetam-like drug which is under development for the treatment of COVID-19, Alzheimer's disease, fragile X syndrome, Rett syndrome, major depressive disorder, and other neurological disorders.[2][3][4] In the case of COVID-19, it is specifically being developed for treatment of COVID-19-induced neuropathy.[5]

Pharmacology

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Pharmacodynamics

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The mechanism of action of traneurocin is either unknown or undisclosed.[6][7] However, it has been described as acting as a positive allosteric modulator of the AMPA receptor and has been found to increase brain-derived neurotrophic factor (BDNF) levels.[2][8][4][9] It has also been found to act as a positive allosteric modulator of the GABAA receptor.[10] The drug is described as having neuroprotective, neurogenesis-stimulating, and pro-cognitive or nootropic effects.[11][12][5][1][4] It has also been reported to have antihypoxic and anxiolytic properties.[13][4]

Pharmacokinetics

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It is known to be an endogenous compound present at micromolar concentrations in the rat brain and readily crosses the blood–brain barrier.[1][4]

Chemistry

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Chemically, traneurocin is a synthetic cyclized dipeptide composed of the amino acids glycine and proline.[3][14][15]

Clinical trials

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As of September 2024, traneurocin is in phase 3 clinical trials for COVID-19, phase 2 clinical trials for Alzheimer's disease, fragile X syndrome, and Rett syndrome, and phase 1 clinical trials for major depressive disorder.[2] No development has been reported for treatment of other neurological disorders.[2] Traneurocin was first developed, under the name cycloprolylglycine (CPG), in Russia in 1991 as a drug related structurally and pharmacologically to piracetam.[13][4][16] Cycloprolylglycine is also related to and known to be the major metabolite of omberacetam (Noopept).[13]

Another drug, vineurocin (NA-704), is also being developed for treatment of Alzheimer's disease.[17][18] This drug is described as a recombinant growth hormone with neuroprotective and neurogenic effects.[19]

See also

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References

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  1. ^ a b c Tran B, Tran L, Vu F (2018). "P4-202: NA-831 as a Regenerative Therapeutic for Alzheimer's Disease: A Phase 1 Safety, Tolerability and Pharmacokinetics Study". Alzheimer's & Dementia. 14 (7S_Part_29). Wiley. doi:10.1016/j.jalz.2018.07.023. ISSN 1552-5260.
  2. ^ a b c d "Traneurocin". AdisInsight. Springer Nature Switzerland AG. 25 September 2024. Retrieved 19 October 2024.
  3. ^ a b "Delving into the Latest Updates on Traneurocin with Synapse". Synapse. 19 September 2024. Retrieved 19 October 2024.
  4. ^ a b c d e f Gudasheva TA, Grigoriev VV, Koliasnikova KN, Zamoyski VL, Seredenin SB (November 2016). "Neuropeptide cycloprolylglycine is an endogenous positive modulator of AMPA receptors". Doklady. Biochemistry and Biophysics. 471 (1): 387–389. doi:10.1134/S160767291606003X. PMID 28058675.
  5. ^ a b Choi HS, Choi AY, Kopp JB, Winkler CA, Cho SK (April 2024). "Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval". Journal of Korean Medical Science. 39 (14): e134. doi:10.3346/jkms.2024.39.e134. PMC 11018982. PMID 38622939.
  6. ^ Dalvi T, Dewangan B, Das R, Rani J, Shinde SD, Vhora N, et al. (2020). "Old Drugs with New Tricks: Paradigm in Drug Development Pipeline for Alzheimer's Disease". Central Nervous System Agents in Medicinal Chemistry. 20 (3): 157–176. doi:10.2174/1871524920666201021164805. PMID 33087034.
  7. ^ Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K (2019). "Alzheimer's disease drug development pipeline: 2019". Alzheimer's & Dementia. 5 (1). Wiley: 272–293. doi:10.1016/j.trci.2019.05.008. PMC 6617248. PMID 31334330.
  8. ^ "NA-831". ALZFORUM. 28 November 2023. Retrieved 19 October 2024.
  9. ^ Gudasheva TA, Koliasnikova KN, Antipova TA, Seredenin SB (July 2016). "Neuropeptide cycloprolylglycine increases the levels of brain-derived neurotrophic factor in neuronal cells". Doklady. Biochemistry and Biophysics. 469 (1): 273–276. doi:10.1134/S1607672916040104. PMID 27599510.
  10. ^ Sharonova IN, Bukanova YV, Gudasheva TA, Skrebitsky VG (May 2019). "Effect of Endogenous Neuropeptide Cycloprolylglycine on GABAA Receptors in Cerebellar Purkinje Cells". Bulletin of Experimental Biology and Medicine. 167 (1): 39–42. doi:10.1007/s10517-019-04455-7. PMID 31177457.
  11. ^ Alavian G, Kolahdouzan K, Mortezazadeh M, Torabi ZS (May 2021). "Antiretrovirals for Prophylaxis Against COVID-19: A Comprehensive Literature Review". Journal of Clinical Pharmacology. 61 (5): 581–590. doi:10.1002/jcph.1788. PMC 7753707. PMID 33217030.
  12. ^ Alipour S, Mahmoudi L, Ahmadi F (March 2023). "Pulmonary drug delivery: an effective and convenient delivery route to combat COVID-19". Drug Delivery and Translational Research. 13 (3): 705–715. doi:10.1007/s13346-022-01251-1. PMC 9580423. PMID 36260223.
  13. ^ a b c Gudasheva TA (2015). "Theoretical grounds and technologies for dipeptide drug development". Russian Chemical Bulletin. 64 (9). Springer Science and Business Media LLC: 2012–2021. doi:10.1007/s11172-015-1112-2. ISSN 1066-5285.
  14. ^ "Cyclo(prolylglycyl): Uses, Interactions, Mechanism of Action". DrugBank Online. 13 June 2005. Retrieved 19 October 2024.
  15. ^ "(S)-Hexahydropyrrolo[1,2-a]pyrazine-1,4-dione". PubChem. Retrieved 19 October 2024.
  16. ^ Gudasheva TA, Vasilevich NI, Zolotov NN, Lezina VP, Rozenberg SG, Kravchenko EV, et al. (1991). "Mechanism of nootropic effect of topological proline-based piracetam analogues". Khim.-Farm. Zh. 25 (6): 12–16.
  17. ^ "Vineurocine". AdisInsight. Springer Nature Switzerland AG. 7 April 2021. Retrieved 19 October 2024.
  18. ^ "Delving into the Latest Updates on Vineurocin with Synapse". Synapse. 28 September 2024. Retrieved 19 October 2024.
  19. ^ "1st NIF Presenting Companies". SachsForum. 18 September 2017. Retrieved 19 October 2024. 2. Our second drug candidate, Vineurocin (NA-704) is a recombinant human growth hormone that modulates the aging process in humans. NA-704 exhibits neuroprotection and neurogenesis, which has been demonstrated as a strong candidate for treatment of Alzheimer's disease and other neurological disorders. The NA-704 Phase 2 will be from from June 2018 to May 2019.
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