Interaction between Mitocholine effect and

deuterium content of water

During Mitocholine action, the succinate-supported mitochondrial H2O2 generation is key for IR-A autophosphorylation. We have shown that rates of H2O2 generation decrease with increase of deuterium content of water. Therefore, use of deuterium depleted water as the excipient in aqueous solutions of Mitocholine improves the anti-amnestic effect of former and provides Mitocholine’s products with superior properties.

References to the Mitocholine

  1. Storozheva ZI, Proshin AT, Sherstnev VV, Storozhevykh TP, Senilova YE, Persiyantseva NA, Pinelis VG, Semenova NA, Zakharova EI, Pomytkin IA. Dicholine salt of succinic acid, a neuronal insulin sensitizer, ameliorates cognitive deficits in rodent models of normal aging, chronic cerebral hypoperfusion, and beta-amyloid peptide-(25-35)-induced amnesia. BMC Pharmacol. 2008 Jan 23;8:1.
  1. Pomytkin NA, Storozheva ZI, Semenova NA, Proshin AT, Sherstnev VV, Varfolomeev SD. [Neuroprotective effect of choline succinate in rats with experimental chronic cerebral ischemia evaluated by cognitive ability tests]. Izv Akad Nauk Ser Biol. 2007 Mar-Apr;(2):183-7. Russian.
  1. Costa-Nunes JP, Cline BH, Araújo-Correia M, Valença A, Markova N, Dolgov O, Kubatiev A, Yeritsyan N, Steinbusch HWM, Strekalova T. Animal models of depression and drug delivery with food as an effective dosing method: evidences from studies with Celecoxib and Dicholine Succinate. Biomed Res Int. 2015; 2015:596126.
  1. Cline BH, Steinbusch HW, Malin D, Revishchin AV, Pavlova GV, Cespuglio R, Strekalova T. The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2. BMC Neurosci. 2012 Sep 18;13:110.
  1. Cline BH, Costa-Nunes JP, Cespuglio R, Markova N, Santos AI, Bukhman YV, Kubatiev A, Steinbusch HW, Lesch KP, Strekalova T. Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression. Front Behav Neurosci. 2015 Feb 26;9:37.
  1. Strekalova T, Costa-Nunes J, Veniaminova E, Kubatiev A, Lesch K-P, Chekhonin VP, Evans MC, Steinbusch HMW. Insulin receptor sensitizer, choline salt of succinic acid, prevents both TLR4 upregulation and affective changes induced by a high-cholesterol diet in mice. Affective Disorders, 2015 (in press).
  1. Pomytkin IA, Semenova NA. Study of the effect of preconditioning with succinic acid salt of choline (1:2) on the disturbances of energy metabolism in the brain during ischemia by 31P NMR in vivo. Dokl Biochem Biophys. 2005 Jul-Aug;403:289-92.
  1. Rychikhin VM, Sariev AK, Pomytkin IA. [Anticonvulsant effect of dicholine succinate on primary generalized epilepsy model in mice]. Eksp Klin Farmakol. 2013;76(3):10-2. Russian.
  1. Sariev AK, Rychikhin VM, Pomytkin IA, Voronina TA. [Antiparkinsonian effect of dicholine succinate on the model of MPTP-induced parkinsonism]. Annals Clin Exp Neurol 2011, 5(4): 33-36. Russian.

References to the Mechanism

  1. Storozhevykh TP, Senilova YE, Persiyantseva NA, Pinelis VG, Pomytkin IA. Mitochondrial respiratory chain is involved in insulin-stimulated hydrogen peroxide production and plays an integral role in insulin receptor autophosphorylation in neurons. BMC Neurosci. 2007 Oct 8;8:84.
  1. Storozheva ZI, Proshin AT, Sherstnev VV, Storozhevykh TP, Senilova YE, Persiyantseva NA, Pinelis VG, Semenova NA, Zakharova EI, Pomytkin IA. Dicholine salt of succinic acid, a neuronal insulin sensitizer, ameliorates cognitive deficits in rodent models of normal aging, chronic cerebral hypoperfusion, and beta-amyloid peptide-(25-35)-induced amnesia. BMC Pharmacol. 2008 Jan 23;8:1.
  1. Pomytkin IA. H2O2 Signalling Pathway: A Possible Bridge between Insulin Receptor and Mitochondria. Curr Neuropharmacol. 2012 Dec;10(4):311-20.
  1. Persiyantseva NA, Storozhevykh TP, Senilova YE, Gorbacheva LR, Pinelis VG, Pomytkin IA. Mitochondrial H2O2 as an enable signal for triggering autophosphorylation of insulin receptor in neurons. J Mol Signal. 2013 Oct 5;8(1):11. doi: 10.1186/1750-2187-8-11.

References to the Deiterium depleted water

  1. Pomytkin IA, Kolesova OE. Relationship between natural concentration of heavy water isotopologues and rate of H2O2 generation by mitochondria. Bull Exp Biol Med. 2006, 142(5):570-2.
  1. Strekalova T, Evans M, Chernopiatko A, Couch Y, Costa-Nunes J, Cespuglio R, Chesson L, Vignisse J, Steinbusch HW, Anthony DC, Pomytkin I, Lesch KP. Deuterium content of water increases depression susceptibility: the potential role of a serotonin-related mechanism. Behav Brain Res. 2015, 277:237-44.