Traneurocin

Last updated

Traneurocin
Traneurocin.svg
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 class Neuroprotective; Neurogenesis stimulant; Cognitive enhancer
Pharmacokinetic data
Elimination half-life 7 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
Formula C7H10N2O2
Molar mass 154.169 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]

Contents

Pharmacology

Pharmacodynamics

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

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

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

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. [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

Related Research Articles

<span class="mw-page-title-main">Excitatory synapse</span> Sort of synapse

An excitatory synapse is a synapse in which an action potential in a presynaptic neuron increases the probability of an action potential occurring in a postsynaptic cell. Neurons form networks through which nerve impulses travels, each neuron often making numerous connections with other cells of neurons. These electrical signals may be excitatory or inhibitory, and, if the total of excitatory influences exceeds that of the inhibitory influences, the neuron will generate a new action potential at its axon hillock, thus transmitting the information to yet another cell.

<span class="mw-page-title-main">Piracetam</span> Chemical compound

Piracetam is a drug that has efficacy in cognitive disorders, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia; sources differ on its usefulness for dementia. Piracetam is sold as a medication in many European countries. Sale of piracetam is not illegal in the United States, although it is not regulated nor approved by the FDA, so it is legally sold for research use only.

<span class="mw-page-title-main">Donepezil</span> Medication used for dementia

Donepezil, sold under the brand name Aricept among others, is a medication used to treat dementia of the Alzheimer's type. It appears to result in a small benefit in mental function and ability to function. Use, however, has not been shown to change the progression of the disease. Treatment should be stopped if no benefit is seen. It is taken by mouth or via a transdermal patch.

<span class="mw-page-title-main">Ampakine</span> Subgroup of AMPA receptor positive allosteric modulators

Ampakines or AMPAkines are a subgroup of AMPA receptor positive allosteric modulators with a benzamide or closely related chemical structure. They are also known as "CX compounds". Ampakines take their name from the AMPA receptor (AMPAR), a type of ionotropic glutamate receptor with which the ampakines interact and act as positive allosteric modulators (PAMs) of. Although all ampakines are AMPAR PAMs, not all AMPAR PAMs are ampakines.

<span class="mw-page-title-main">CX717</span> Ampakine

CX717 is an ampakine compound created by Christopher Marrs and Gary Rogers in 1996 at Cortex Pharmaceuticals. It affects the neurotransmitter glutamate, with trials showing the drug improves cognitive functioning and memory.

Racetams, also sometimes known simply as pyrrolidones, are a class of drugs that share a pyrrolidone nucleus. Many, but not all, specifically have a 2-oxo-1-pyrrolidine acetamide (piracetam) nucleus. Some racetams, such as piracetam, aniracetam, oxiracetam, pramiracetam, and phenylpiracetam, are considered nootropics. Phenylpiracetam is also a stimulant. Others, such as levetiracetam, brivaracetam, and seletracetam, are anticonvulsants.

<span class="mw-page-title-main">Phenylpiracetam</span> Chemical compound

Phenylpiracetam, also known as fonturacetam and sold under the brand names Phenotropil, Actitropil, and Carphedon among others, is a stimulant and nootropic medication used in Russia and certain other Eastern European countries in the treatment of cerebrovascular deficiency, depression, apathy, and attention, and memory problems, among other indications. It is also used in Russian cosmonauts to improve physical, mental, and cognitive abilities. The drug is taken by mouth.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.

<span class="mw-page-title-main">Neuromodulation</span> Regulation of neurons by neurotransmitters

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfiguring synaptic connectivity.

<span class="mw-page-title-main">Ispronicline</span> Chemical compound

Ispronicline is an experimental drug which acts as a partial agonist at neural nicotinic acetylcholine receptors. It progressed to phase II clinical trials for the treatment of dementia and Alzheimer's disease, but is no longer under development.

<i>N</i>-Phenylacetyl-<small>L</small>-prolylglycine ethyl ester Prodrug

N-Phenylacetyl-l-prolylglycine ethyl ester is promoted as a nootropic and is a prodrug of cyclic glycine-proline. Other names include the brand name Noopept, developmental code GVS-111, and proposed INN omberacetam.

<span class="mw-page-title-main">Brexpiprazole</span> Atypical antipsychotic

Brexpiprazole, sold under the brand name Rexulti among others, is an atypical antipsychotic medication used for the treatment of major depressive disorder, schizophrenia, and agitation associated with dementia due to Alzheimer's disease.

<span class="mw-page-title-main">ALTO-100</span> BDNF-modulating drug for depression and PTSD

ALTO-100, previously known as NSI-189, is a drug described as a hippocampal neurogenesis stimulant and indirect brain-derived neurotrophic factor (BDNF) modulator which is under development for the treatment of major depressive disorder (MDD), bipolar depression, and post-traumatic stress disorder (PTSD). There has also been interest in ALTO-100 for possible treatment of cognitive impairment and neurodegeneration. It is taken by mouth.

<span class="mw-page-title-main">Blarcamesine</span> Medication

Blarcamesine is an experimental drug which is under development for the treatment of Alzheimer's disease and a variety of other indications.

<span class="mw-page-title-main">AMPA receptor positive allosteric modulator</span>

AMPA receptor positive allosteric modulators are positive allosteric modulators (PAMs) of the AMPA receptor (AMPR), a type of ionotropic glutamate receptor which mediates most fast synaptic neurotransmission in the central nervous system.

<span class="mw-page-title-main">Phenserine</span> Chemical compound

Phenserine is a synthetic drug which has been investigated as a medication to treat Alzheimer's disease (AD), as the drug exhibits neuroprotective and neurotrophic effects.

<span class="mw-page-title-main">Dalzanemdor</span> Chemical compound

Dalzanemdor is experimental drug being investigated for the treatment of neurological disorders and cognitive impairment. It acts as a positive allosteric modulator of the NMDA receptor, whose activity is essential for learning, memory, and cognition. Dalzanemdor is an analogue of the neurosteroid 24S-hydroxycholesterol.

<span class="mw-page-title-main">Glovadalen</span> D1 receptor positive allosteric modulator under development for Parkinsons disease

Glovadalen (developmental code name UCB-0022) is a dopamine D1 receptor positive allosteric modulator which is under development for the treatment of Parkinson's disease. It has been found to potentiate the capacity of dopamine to activate the D1 receptor by 10-fold in vitro with no actions on other dopamine receptors. As of May 2024, glovadalen is in phase 2 clinical trials for this indication. The drug is under development by UCB Biopharma. It is described as an orally active, centrally penetrant small molecule.

ACD856, or ACD-856, is a tropomyosin receptor kinase TrkA, TrkB, and TrkC positive allosteric modulator which is under development for the treatment of Alzheimer's disease, depressive disorders, sleep disorders, and traumatic brain injuries. It is taken by mouth.

<span class="mw-page-title-main">Alogabat</span> GABAA receptor modulator

Alogabat is an α5 subunit-containingGABAA receptor positive allosteric modulator which is under development for the treatment of pervasive developmental disorders and Angelman syndrome. It is taken by mouth.

References

  1. 1 2 3 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. 1 2 3 4 "Traneurocin". AdisInsight. Springer Nature Switzerland AG. 25 September 2024. Retrieved 19 October 2024.
  3. 1 2 "Delving into the Latest Updates on Traneurocin with Synapse". Synapse. 19 September 2024. Retrieved 19 October 2024.
  4. 1 2 3 4 5 6 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. 1 2 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. 1 2 3 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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.