Choline Donors

Active forms of choline donors that work through different pathways in the peripheral and central nervous system to support acetylcholine levels, along with the other synergistically stacked cholinergics (e.g., acetyl donors, acetylcholinesterase inhibitors, racetamic compounds).


Choline Donors - Centrophenoxine

Centrophenoxine

Overview:
Centrophenoxine is a cholinergic compound with long-term neuroprotective and nootropic activity. Studies indicate that centrophenoxine can improve working memory and be a general memory enhancer.

Scientific Name:
2-Dimethylaminoethyl(4-chlorophenoxy)acetate

Mechanisms:

  • Increases the levels of Acetylcholine in the brain[1]
  • Anti-aging effects[2]
  • Decreases the accumulation of cellular waste and toxins in the brain[3]
  • Antioxidant effect – decreases lipid peroxidation
  • Increases RNA and protein synthesis in the brain[4]
  • Increases glucose uptake in neurons and glia[5]
  • Decreases cognitive decline by reducing cellular dehydration[6]
  • Increases synaptic connections – improved neuronal communication[7]
References

[1] Wood PL & Péloquin A (1982). Increases in choline levels in rat brain elicited by meclofenoxate. Neuropharmacology, 21(4):349-54. doi: 10.1016/0028-3908(82)90099-5
[2] Bhalla P & Nehru B (2005). Modulatory effects of centrophenoxine on different regions of ageing rat brain. Exp Gerontol, 40(10):801-6. doi: 10.1016/j.exger.2005.06.016
[3] Nehru B1 & Bhalla P (2006). Reversal of an aluminium induced alteration in redox status in different regions of rat brain by administration of centrophenoxine. Mol Cell Biochem, 290(1-2):185-91. doi: 10.1007/s11010-006-9186-7
[4] Sharma D, et al (1993). Age-related decline in multiple unit action potentials of CA3 region of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxine. Neurobiol Aging, 14(4):319-30. doi: 10.1016/0197-4580(93)90117-T
[5] Watanabe S, et al (1975). Effects of various cerebral metabolic activators on glucose metabolism of brain. Folia Psychiatr Neurol Jpn, 29(1):67-76. doi: 10.1111/j.1440-1819.1975.tb02324.x
[6] Zs-Nagy I (1989). On the role of intracellular physicochemistry in quantitative gene expression during aging and the effect of centrophenoxine. A review. Arch Gerontol Geriatr, 9(3):215-29. doi: 10.1016/0167-4943(89)90042-3
[7] Bertoni-Freddari C, et al (1982). The effect of acute and chronic centrophenoxine treatment on the synaptic plasticity of old rats. Arch Gerontol Geriatr, 1(4):365-73. doi: 10.1016/0167-4943(82)90036-X

Choline Donors - Citicoline

Citicoline

Overview:
CDP Choline is a compound made up of choline and cytidine with neuroprotective and nootropic activity. CDP Choline decreases age-related memory impairment and cognitive decline, and enhances attention, learning and memory.

Scientific Name:
Cytidine diphosphocholine

Mechanisms:

  • After ingestion, CDP Choline originates choline and cytidine, the latter then being converted into uridine[1]
  • Both choline and uridine are neuroprotective[1]
  • Choline is a nicotinic Acetylcholine receptor agonist[2]
  • Increases the production of acetylcholine, adrenalin and noradrenalin[1]
  • Increases the release of Dopamine by acting on dopamine transporters[3]
  • Increases phosphatidylcholine production in the brain – an important component of cell membranes[4]
  • Maintains neuronal membrane integrity and reduces neuronal death[4,5]
References

[1] Weiss GB1 (1995). Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. Life Sci. 1995;56(9):637-60. doi: 10.1016/0024-3205(94)00427-T
[2] Levin ED (2013). Complex relationships of nicotinic receptor actions and cognitive functions. Biochem Pharmacol, 86(8):1145-52. doi: 10.1016/j.bcp.2013.07.021
[3] Tayebati SK, et al (2013). Modulation of monoaminergic transporters by choline-containing phospholipids in rat brain. CNS Neurol Disord Drug Targets, 12(1):94-103. doi: 10.2174/1871527311312010015
[4] Fagone P & Jackowski S (2012). Phosphatidylcholine and the CDP-choline cycle. Biochim Biophys Acta, 1831(3):523-32. doi: 10.1016/j.bbalip.2012.09.009
[5] Dempsey RJ & Raghavendra Rao VL (2003). Cytidinediphosphocholine treatment to decrease traumatic brain injury-induced hippocampal neuronal death, cortical contusion volume, and neurological dysfunction in rats. J Neurosurg, 98(4):867-73. doi: 10.3171/jns.2003.98.4.0867

Choline Donors - Alpha GPC

Alpha GPC

Overview:
Alpha-GPC is a compound made up of choline and glycerophosphate with neuroprotective activity. Alpha-GPC prevents cognitive decline, and increases attention and memory.

Scientific Name:
Alpha-glycerophosphocholine

Mechanisms:

  • Dissociates into choline and the phospholipid glycerophosphate after ingestion[1]
  • The most effective cholinergic in increasing choline levels in the brain[2]
  • Choline is a nicotinic Acetylcholine receptor agonist[3]
  • Increases the production of acetylcholine[1]
  • Increases cell membrane phospholipid production, namely phosphatidylcholine[1]
  • Maintains neuronal membrane integrity[4]
  • Increases potassium-invoked calcium release and dopamine release[5,6]
  • Can increase growth hormone production[7]
References

[1] Abbiati G, et al (1993). Absorption, tissue distribution and excretion of radiolabelled compounds in rats after administration of [14C]-L-alpha-glycerylphosphorylcholine. Eur J Drug Metab Pharmacokinet, 18(2):173-80. doi: 10.1007/BF03188793
[2] Gatti G, et al (1992). A comparative study of free plasma choline levels following intramuscular administration of L-alpha-glycerylphosphorylcholine and citicoline in normal volunteers. Int J Clin Pharmacol Ther Toxicol, 30(9):331-5. PMID: 1428296
[3] Levin ED (2013). Complex relationships of nicotinic receptor actions and cognitive functions. Biochem Pharmacol, 86(8):1145-52. doi: 10.1016/j.bcp.2013.07.021
[4] Klein J (2000). Membrane breakdown in acute and chronic neurodegeneration: focus on choline-containing phospholipids. J Neural Transm (Vienna), 107(8-9):1027-63. doi: 10.1007/s007020070051
[5] Schettini G, et al (1992). Molecular mechanisms mediating the effects of L-alpha-glycerylphosphorylcholine, a new cognition-enhancing drug, on behavioral and biochemical parameters in young and aged rats. Pharmacol Biochem Behav, 43(1):139-51. doi: 10.1016/0091-3057(92)90650-5
[6] Trabucchi M, et al (1986). Changes in the interaction between CNS cholinergic and dopaminergic neurons induced by L-alpha-glycerylphosphorylcholine, a cholinomimetic drug. Farmaco Sci. 1986 Apr;41(4):325-34. PMID: 3709792
[7] Ceda GP, et al (1992). alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects. Horm Metab Res, 24(3):119-21. doi: 10.1055/s-2007-1003272