Inosine
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Inosine is a
Knowledge of inosine metabolism has led to advances in
Reactions
Purine nucleoside phosphorylase intraconverts inosine and hypoxanthine.
Inosine is also an intermediate in a chain of purine nucleotide reactions required for muscle movements.
Clinical significance
In the 1970s, inosine was used by athletes in Eastern countries in an attempt to improve performance.[citation needed] Subsequent studies in humans suggest that inosine supplementation has no effect on athletic performance.[2] Animal studies have suggested that inosine has neuroprotective properties. It has been proposed for spinal cord injury[3] and for administration after stroke, because observation suggests that inosine induces axonal rewiring.[4]
After ingestion, inosine is metabolized into uric acid, which has been suggested to be a natural antioxidant and peroxynitrite scavenger with potential benefits to patients with multiple sclerosis (MS).[5] Peroxynitrite has been correlated with axon degeneration [6] In 2003, a study was initiated at the University of Pennsylvania MS Center to determine whether raising the levels of uric acid by the administration of inosine would slow the progression of MS.[7] The study was completed in 2006 but the results were not reported to NIH. A subsequent publication hinted at potential benefits but the sample size (16 patients) was too small for a definitive conclusion.[8] In addition, the side effect of the treatment was the development of kidney stones in four of 16 patients.[citation needed]
With phase II trials for Parkinson's disease completed, inosine will continue to phase III trials. Earlier trials suggested that patients with the highest serum urate levels had slower progression of Parkinson's symptoms. The trial uses inosine to raise urate levels in those with levels lower than the population mean (6 mg/dL).[9][10][11]
Alseres Pharmaceuticals (named Boston Life Sciences when patent was granted) patented the use of inosine to treat stroke[12] and was investigating the drug in the MS setting.[13]
In the Anatomical Therapeutic Chemical Classification System, it is classified as an antiviral.[14]
Binding
Inosine is a natural ligand for the benzodiazepine binding site on the GABA A receptor.[15]
Biotechnology
When designing primers for polymerase chain reaction, inosine is useful in that it can pair with any natural base.[16] This allows for design of primers that span a single-nucleotide polymorphism, without the polymorphism disrupting the primer's annealing efficiency.
However, inosine pairs preferentially with cytosine (C) and its introduction to RNA, e.g. by the action of ADARs, thereby destabilizes double-stranded RNA by changing AU base-pairs to IU mismatches.[17]
Fitness
Despite lack of clinical evidence that it improves muscle development, inosine remains an ingredient in some fitness supplements.
Feeding stimulant
Inosine has also been found to be an important feed stimulant by itself or in combination with certain
See also
- Inosine monophosphate dehydrogenase
- Inosine pranobex
- Nucleobase
References
- PMID 33921764.
- PMID 30068354.
- PMID 16317421.
- PMID 12084941.
- ^ "Uric Acid In Multiple Sclerosis". WebCite. 2018. Archived from the original on 2009-10-27.
- ^ Neuhaus O, Hartung HO. "Immune mediated injury, oxidative toxicity and excitotoxicity in multiple sclerosis. Possibilities for immune modulation and neuroprotection". Archived from the original on 2007-03-11. Retrieved 2006-04-23.
- ^ Clinical trial number NCT00067327 for "Treatment of Multiple Sclerosis Using Over the Counter Inosine" at ClinicalTrials.gov
- PMID 19425822.
- ^ "Safety of Urate Elevation in Parkinson's Disease". Fox Trial Finder. 2018.
- ^ Clinical trial number NCT00833690 for "Safety of Urate Elevation in Parkinson's Disease" at ClinicalTrials.gov
- ^ Kuhl MM (September 1, 2015). "Inosine Trial Secures Phase III Funding to Study Effect on Slowing Parkinson's". Michael J. Fox Foundation.
- ^ "Boston Life Sciences Announces Issuance of Inosine Patent for Treatment of Spinal Cord Injury". November 17, 2003. Archived from the original on 2005-09-03.
- .
- ^ "ATC/DDD Index". World Health Organization Collaborating Centre. Retrieved Dec 20, 2017.
- PMID 9691220.
- PMID 16950904.
- S2CID 11698374.
- ^ Mackie AM (1987). "Identification of the gustatory feeding stimulants.". In Hara TJ (ed.). Chemoreception in Fishes. Amsterdam: Elsevier Scientific Publishing Co. pp. 275–291.
- .