(Hypoxanthine Riboside, Hypoxanthosine)
Orally, Inosine is used for enhancing athletic performance.
Preliminary evidence suggests Inosine might stimulate axon growth from uninjured nerve cells to injured nerve cells of the central nervous system. Further studies in humans are needed to establish whether this finding has significance in restoring function after spinal cord injuries
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Published Clinical Studiescs
Inosine reduces ischemic brain injury in rats.1
Shen H, Chen GJ, Harvey BK, Bickford PC, Wang Y.
National Institute on Drug Abuse, National Institutes of Health, Baltimore, Md, USA.
BACKGROUND AND PURPOSE: Purinergic nucleoside inosine elicits protection and regeneration during various injuries. The purpose of this study was to examine the protective effects of inosine against cerebral ischemia. METHODS: Adult Sprague-Dawley rats were anesthetized. Inosine, hypoxathine, or vehicle was administered intracerebroventricularly before transient right middle cerebral artery occlusion (MCAo). Animals were placed in behavioral chambers 2 days to 2 weeks after MCAo and then euthanized for tri-phenyl-tetrazolium chloride staining. Glutamate release was measured by microdialysis/high-performance liquid chromatography, and single-unit action potentials were recorded from neurons in the parietal cortex. RESULTS: Stroke animals receiving inosine pretreatment demonstrated a higher level of locomotor activity and less cerebral infarction. Intracerebroventricular administration of the same dose of hypoxanthine did not confer protection. Coadministration of selective A3 receptor antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191) significantly reduced inosine-mediated protection. Inosine did not alter basal glutamate release, nor did it reduce ischemia-evoked glutamate overflow from cerebral cortex. However, inosine antagonized glutamate-induced electrophysiological excitation in cerebral cortical neurons. CONCLUSIONS: Inosine inhibits glutamate postsynaptic responses and reduces cerebral infarction. Its protective effect against ischemia/reperfusion-related insults may involve activation of adenosine A3 receptors.
PMID: 15692110 [PubMed - in process]
Inosine : a naturally occurring cardiotonic agent.2
Aviado DM.
For many years, Inosine was considered to be a simple metabolite of adenosine which was devoid of any cardiovascular effects. This theoretical ineffectiveness can be explained in the light of recent studies by the use of inadequate doses. In fact, higher doses of inosine, a non-toxic nucleoside, have demonstrated, experimentally, a cardiovascular activity and the pharmacological profile of this naturally occurring substance has been defined. Like adenosine, inosine is a potent coronary vasodilator. The vasodilatation induced by inosine is only partly due to increased metabolic demands. Inosine has a direct action on coronary artery relaxation independent of the inotropic effect. It alters the balance between oxygen supply and demand which is reflected by an intramyocardial redistribution of oxygen in favour of the sub-endocardial zones. Inosine acts on the coronary circulation like a "regulator of myocardial nutrition", unlike adenosine, which can be thought of as a "coronary vasoregulator". This dissociation between the two nucleosides is apparently due to different vascular sites of action. The positive inotropic action of inosine, which has been demonstrated in both healthy and pathological myocardium in all of the experimental animal species studied, is not due to stimulation of the cardiac beta-adrenergic receptors, as beta-blockers do not antagonize the positive inotropic effect of inosine. This increase in myocardial contractile dynamics is evident in infarcted as well as healthy areas of myocardium. The inotropic and coronary vasodilator effects of inosine are not associated with any modification of the chronotropic function. Inosine is not arrhythmogenic, even at high doses. Furthermore, it does not affect atrioventricular conduction. It has been demonstrated that inosine is capable of antagonizing ouabain induced arrhythmias. Various clinical studies confirm the positive inotropic action of inosine, without any alteration in the post-load, the pre-load or the heart rate. The positive inotropic action of inosine can therefore be considered to be selective. Together with these haemodynamic effects, it has been shown that the addition of inosine to cardioplegic solutions improves the functional recovery of the myocardium, by increasing the quantity of energy-rich phosphates. Similar beneficial results have been obtained in renal transplantation, both experimentally and in clinical studies. The mechanism of action of inosine remains unknown. Are the haemodynamic effects of this compound due to its metabolic effects? Are there specific myocardial purinergic receptors? (ABSTRACT TRUNCATED AT 400 WORDS)
Publication Types:
Review
Suppression of food intake by adenosine and inosine.3
Capogrossi MC, Francendese A, DiGirolamo M.
The effect of adenosine and inosine on food consumption was tested by a 4 hr satiety assay in rats fasted overnight who then received injections subcutaneously, and also in ad libitum fed rats infused intravenously for 24 hr periods. It was found that adenosine, and to a lesser degree inosine, produced a significant suppression of food intake (86 and 69% reduction from control, respectively) during the 1st hr after subbcutaneous injection. This effect persisted for 4 hr, at the end of which both substances produced an average 37% reduction in food intake from control values. This effect of adenosine was also found in ad libitum-fed animals infused intravenously with adenosine for 24 hr (35% reduction from control). These studies report a previously undescribed effect of adenosine and add another substance to the list of agents shown to influence food intake regulation. Since adenosine is known to play a local regulatory role on adipose tissue metabolism and is generated and released from adipose tissue, the present findings may indicate an additional role for adenosine in providing a feedback regulatory signal between the adipose organ and the hypothalamic centers of food intake regulation.
PMID: 474465 [PubMed - indexed for MEDLINE]
Uptake and utilization of nucleosides for energy repletion.4
Giannecchini M, Matteucci M, Pesi R, Sgarrella F, Tozzi MG, Camici M.
Dipartimento di Fisiologia e Biochimica, Via S. Zeno 51, 56127 Pisa, Italy.
In this paper, we report that cells undergoing metabolic stress conditions may use the ribose moiety of nucleosides as energy source to slow down cellular damage. In fact, the phosphorolytic cleavage of the N-glycosidic bond of nucleosides generates, without energy expense, the phosphorylated pentose, which through pentose phosphate pathway and glycolysis, can be converted to energetic intermediates. In this respect, nucleosides may be considered as energy source, alternative or supplementary to glucose, which may become of primary importance especially in conditions of cellular stress. In accordance with the role of these compounds in energy repletion, we also show that the uptake of nucleosides is increased when the energetic demand of the cell is enhanced. As cell model, we have used a human colon carcinoma cell line, LoVo, and the depletion of ATP, with a concomitant fall in the cell energy charge, has been induced by exclusion of glucose from the medium and pre-incubation with oligomycin, an inhibitor of oxidative phosphorylation. In these conditions of energy starvation, we show that the uptake of 2'-deoxyadenosine in LoVo cells is significantly enhanced, and that the phosphorylated ribose moiety of inosine can be used for energy repletion through anaerobic glycolysis. Our data support previous reports indicating that the phosphorylated ribose stemming from the intracellular catabolism of nucleosides may be used in eukaryots as energy source, and advance our knowledge on the regulation of the uptake of nucleosides in eukaryotic cells.
PMID: 15694839 [PubMed - in process]
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