TABLE 1.

Summary of in vitro, preclinical and clinical studies that have demonstrated the therapeutic potential of inosine to treat neurological and psychiatric diseases.

CNS disorder	Specie	Agent	Dose/Concentration/Route	Effect	References
Pain	Mice	Inosine	10–300 mg/kg/i.p. and p.o. 10 μg/i.c.v./i.t.	Inosine mediates reduction time of licking in the formalin test, inhibition of glutamate-induced nociception, reduction mechanical allodynia and hyperalgesia	Nascimento et al., 2010
Pain	Mice	Inosine	10 mg/kg/i.p.	Inosine promotes antinociception through pertussis toxin sensitive G-protein coupled receptors and voltage gated K+ channel, large conductance Ca2+-activated and ATP-sensitive K+ channels or inactivation of voltage-gated Ca2+ channels	Macedo-Junior et al., 2013
Pain	Mice	Inosine	10 and 100 mg/kg/i.p	Inosine reduces flinching behavior induced by formalin and systemic and central nociception in A1-wild type mice	Nascimento et al., 2015
Pain	Mice	Inosine	200–600 nmol/i.t.	Inosine inhibits nociceptive response induced by injection of capsaicin and increases ATP, ADP, AMP, adenosine, inosine, hypoxanthine, xanthine, and uric acid CSF levels	de Oliveira et al., 2016
Learning and memory	Rat	Inosine	100 and 200 mg/kg/i.p.	Learning and memory improvement, levels of TNF-alpha reduction, antioxidant properties increment	Ruhal and Dhingra, 2018
Epilepsy	Rat	Inosine	500 and 1000 mg/kg, i.p.	Inosine increases number and total time of spike-waves discharges	Kovács et al., 2015a, b
Epilepsy	Mice	Inosine	400 nmol/4 μl, i.c.v.	Inosine protect against quinolinic-acid induced seizures	Ganzella et al., 2011
Alzheimer	Rat	Inosine	100 mg/kg, i.c.v.	Inosine induces memory deficit prevention and AChE activity reduction	Teixeira et al., 2020
Parkinson	Dopaminergic cells culture	Inosine	—	H2O2-toxic effect on dopaminergic cells reduction, indicators of free radical generation and oxidative damage in MES 23.5-astrocytes co-cultures were reduced	Cipriani et al., 2010
Parkinson	Human	Inosine	500 mg; p.o.	Average serum urate increment (more pronounced in woman), reduction of motor symptoms in UPDRS scale	Schwarzschild et al., 2019
Neural regeneration	Goldfish	Inosine	50 and 100 μM	Inosine increases retinal ganglion cells neuronal outgrowth and GAP-43 levels	Petrausch et al., 2000
Neural regeneration	PC12 cells and neuronal embryonic cells Sprague-Dawley rat fetuses	Inosine	100 μM – 1 mM	Inosine activates Mst3b kinase activity	Irwin et al., 2006
Anxiety	Mice	Inosine	10 – 300 mg/kg, i.p.	Inosine antagonizes anxiety-reducing actions of benzodiazepines	Crawley et al., 1981
Anxiety	Mice	Inosine	10 – 60 mg/kg, s.c.	Inosine presents anxiolytic effect in the Vogel-type anti-conflict test	Okuyama et al., 1998
Depression	Mice	Inosine	10 mg/kg, i.p.	Inosine reduces mice immobility time in the forced swim test and in the tale suspension test	Kaster et al., 2013
Depression	Human	Inosine plasma levels	—	Inosine plasma levels are significantly higher in individuals treated with antidepressant drugs when compared to healthy individuals	Zhou et al., 2019