Traneurocin Explained

Class:Neuroprotective
Neurogenesis stimulant; Cognitive enhancer
Elimination Half-Life:7 hours
Cas Number:3705-27-9
Pubchem:126154
Drugbank:DB04541
Chemspiderid:112149
Unii:W7O69J5F2B
Chembl:360216
Synonyms:Cycloprolylglycine; 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
Iupac Name:(8aS)-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
C:7
H:10
N:2
O:2
Smiles:C1C[C@H]2C(=O)NCC(=O)N2C1
Stdinchi:1S/C7H10N2O2/c10-6-4-8-7(11)5-2-1-3-9(5)6/h5H,1-4H2,(H,8,11)/t5-/m0/s1
Stdinchikey: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.[1] [2] [3] In the case of COVID-19, it is specifically being developed for treatment of COVID-19-induced neuropathy.

Pharmacology

Pharmacodynamics

The mechanism of action of traneurocin is either unknown or undisclosed.[4] [5] 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.[6] [7] It has also been found to act as a positive allosteric modulator of the GABAA receptor.[8] The drug is described as having neuroprotective, neurogenesis-stimulating, and pro-cognitive or nootropic effects.[9] [10] [11] [12] It has also been reported to have antihypoxic and anxiolytic properties.

Pharmacokinetics

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

Chemistry

Chemically, traneurocin is a synthetic cyclized dipeptide composed of the amino acids glycine and proline.[13] [14]

Clinical trials

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. No development has been reported for treatment of other neurological disorders. Traneurocin was first developed, under the name cycloprolylglycine (CPG), in Russia in 1991 as a drug related structurally and pharmacologically to piracetam.[15] [16] Cycloprolylglycine is also related to and known to be the major metabolite of omberacetam (Noopept).

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

External links

Notes and References

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