Endogenous Metabolite; alpha7 nicotinic receptors

Choline chloride (0 or 70 μM, 4 days) is beneficial in proving cell survival and preserving cell viability [1].

Choline chloride (sc, 0.2 and 100 mg/kg/h, 24 or 48 hours) can efficiently lower the release of tumor factor (TNF) from macrophages and lessen the detrimental response of female C57/Bl6 studies [2].

Cell Viability Assay[1]
Cell Types: rat pheochromocytoma cells PC12
Tested Concentrations: 0 or 70 μM
Incubation Duration: 4 days
Experimental Results: Cell viability was 94% at 70 μM and 83% at 0 μM. Compared with the no-treatment group, the number of cells showing DNA fragmentation (a characteristic of apoptosis) was diminished by 8.5% at 70 μM.

Animal/Disease Models: Female C57/Bl6 mouse postoperative pain model [2]
Doses: 0.2 and 100 mg/kg/h
Route of Administration: subcutaneous injection, 24 or 48 hrs (hrs (hours))
Experimental Results: Heat allergy was diminished after surgery, and maximum efficacy was achieved after 48 hrs (hrs (hours)) of treatment . The ED50 value of the choline dose is 1.7 mg/kg/h. Allergic responses to punctate mechanical stimulation were diminished in a dose-dependent manner with an ED50 value of 4.7 mg/kg/h at 48 hrs (hrs (hours)) but not at 24 hrs (hrs (hours)) after infusion.

Absorption, Distribution and Excretion
This study investigated the pharmacokinetics of choline in four patients receiving long-term total parenteral nutrition. Over several consecutive days, each subject received intravenous infusions of 7, 14, 28, and 56 mmol of choline chloride over 12 hours. Plasma choline concentrations were measured at baseline, 1/4, 1, 3, 6, and 12 hours after infusion, and 3 and 12 hours after the end of infusion. 24-hour urine samples were collected daily for analysis. Analysis of variance showed that the data from all four subjects conformed to a two-compartment model, with saturated elimination in the central compartment. The two-compartment model was significantly superior to the one-compartment model in all subjects (p < 10⁻⁸ in all cases), and significantly superior to the unsaturated model in three of the four subjects (p = 1.0 x 10⁻⁹, 7.5 x 10⁻⁶, and 9.4 x 10⁻¹¹, respectively). This model can estimate the rate constant of choline elimination at ambient concentrations, the first-order rate constant of transport between the central and peripheral compartments, the dissociation constant of the saturated elimination process, the apparent volume of distribution in the central compartment, the steady-state volume of distribution, and the choline content in the central compartment and the easily exchangeable pool. Choline chloride is a strong base with surprisingly high absorption at pH 7, but lower absorption at lower pH values. Choline can be absorbed from the diet, either as choline itself or as lecithin. The latter is hydrolyzed by the intestinal mucosa to glycerophosphate choline, which either enters the liver to release choline or is transported to peripheral tissues via the intestinal lymphatic system. /Choline/ Choline chloride (1-2 g, four times daily, increasing the dose every two days, with a maximum dose of 2-5 g, four times daily, orally) can dose-dependently increase serum choline levels in patients with Huntington's disease and increase cerebrospinal fluid choline levels, but is independent of serum levels. For more complete data on the absorption, distribution, and excretion of choline chloride (11 types), please visit the HSDB records page.

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Metabolism/Metabolites
Free choline is not completely absorbed, especially after high doses, as intestinal bacteria metabolize it into trimethylamine. Choline
The human body can synthesize choline de novo, primarily in the liver, through the methylation of phosphatidylethanolamine using S-adenosylmethionine as a methyl donor. This means that some choline needs can be met by methyl groups produced through one-carbon metabolism (via methylfolate and methionine). Many vitamins (folate, vitamin B12, vitamin B6, and riboflavin) and the amino acid methionine interact with choline in one-carbon metabolism…Methionine, methyltetrahydrofolate (THF), and choline can serve as alternative sources of methyl groups. Choline
Before being absorbed by the intestines, some choline is metabolized by bacteria into betaine and methylamine (methylamine is not a methyl donor)... Although some free choline is excreted in urine, most is oxidized in the kidneys to form betaine... Choline
Acetylcholine is one of the most important neurotransmitters used by neurons in the brain's memory centers (hippocampus and septum). Choline accelerates the synthesis and release of acetylcholine in nerve cells. The choline used by brain neurons mainly comes from membrane lecithin (phosphatidylcholine), or from dietary choline and lecithin... When extracellular choline supply is insufficient, lecithin-derived choline may be particularly important, for example, in elderly individuals due to reduced brain choline uptake leading to insufficient extracellular choline supply... /Choline/
For more complete data on the metabolism/metabolites of choline chloride (6 types), please visit the HSDB record page.

Maximum drug dose
The upper limit of tolerance for choline is set at 3 g/day.
Coates, PM, Blackman, MR, Cragg, GM, Levine, M., Moss, J., White, JD (eds.), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, p. 109 (2005)
The tolerable upper intake level (UL) for adults is 3.5 g/day.

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Interactions
Repeated administration of choline chloride to female rats exacerbates carbon tetrachloride-induced liver necrosis. LEDDA GM et al.; RASS MED SARDA 80(4) 215 (1977)
Lithium administration enhances the effect of exogenous choline on brain acetylcholine levels.

[1]. Apoptosis is induced by choline deficiency in fetal brain and in PC12 cells. Brain Res Dev Brain Res. 1997 Jul 18;101(1-2):9-16.

[2]. Antinociceptive and anti-inflammatory effects of choline in a mouse model of postoperative pain. Br J Anaesth. 2010 Aug;105(2):201-7.

Choline chloride is a white crystalline solid, and its aqueous solution is almost neutral. (NTP, 1992)
Choline chloride is a quaternary ammonium salt composed of choline cations and chloride ions. It is an animal growth promoter. It is both a chloride and a quaternary ammonium salt. It contains choline.
Choline is a basic component of lecithin, which is found in many animal and plant organs. It acts as a precursor to acetylcholine, a methyl donor in various metabolic processes, and an important component in lipid metabolism.
Mechanism of Action

Choline plays multiple roles in the body. It is an important component of phospholipids, affects the mobilization of hepatic fat (lipophilic action), acts as a methyl donor, and is essential for the formation of the neurotransmitter acetylcholine. /Choline/
Several mechanisms are thought to explain the cancer-promoting effects of a choline-deficient diet. These changes include: increased cell proliferation related to regeneration after parenchymal cell death in choline-deficient livers; DNA hypomethylation (altering gene expression); increased hepatic lipid peroxidation due to mitochondrial reactive oxygen species leakage; activation of the protein kinase C signaling pathway due to diacylglycerol accumulation in the liver; mutations in the tumor suppressor gene Fragile Histidine Triad (FHIT); and defects in apoptosis mechanisms. Loss of phosphatidylethanolamine N-methyltransferase (PEMT) function may also lead to malignant transformation of hepatocytes. /Choline/
Acetylcholine is one of the most important neurotransmitters used by neurons in the brain's memory centers (hippocampus and septum). Choline accelerates the synthesis and release of acetylcholine in nerve cells. Choline/
Female Sprague-Dawley rats were given approximately 300 mg/kg of choline chloride daily via drinking water from day 11 of gestation to parturition, and nerve growth factor (NGF) levels in their hippocampus and frontal cortex were measured in their male offspring at 20 and 90 days of age. Prenatal choline supplementation significantly increased hippocampal NGF levels at 20 and 90 days of age, while choline-supplemented rats showed increased NGF levels in the frontal cortex at 20 days of age, but no increase at 90 days of age. These results suggest that elevated NGF levels during development or adulthood may be one of the potential mechanisms by which perinatal exposure to high concentrations of choline chloride improves spatial and temporal memory in adult rats.

C5H14CLNO

139.6238

139.076

67-48-1

Choline bitartrate;87-67-2;Choline Fenofibrate;856676-23-8;Choline-d4 chloride;285979-70-6;Choline-d9 chloride;61037-86-3;Choline Chloride-13C3;Choline theophyllinate;4499-40-5;Glycerophosphoinositol choline;425642-32-6;Choline-d6 chloride;Choline-d13 chloride;352438-97-2;Choline-13C2 chloride;202190-49-6; 425642-32-6 (choline); 129830-95-1 (free); 425642-29-1 (potassium); 425642-30-4 (sodium)

6209

White to off-white solid powder

1.205 g/cm3

302-305 °C (dec.)(lit.)

1

2

2

8

46.5

0

SGMZJAMFUVOLNK-UHFFFAOYSA-M

InChI=1S/C5H14NO.ClH/c1-6(2,3)4-5-7;/h7H,4-5H2,1-3H3;1H/q+1;/p-1

2-hydroxyethyl(trimethyl)azanium;chloride

CHOLINE CHLORIDE; 67-48-1; Hepacholine; Lipotril; Paresan; 2-Hydroxy-N,N,N-trimethylethanaminium chloride; Hormocline; (2-Hydroxyethyl)trimethylammonium chloride;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 140 mg/mL (~1002.72 mM)
H2O : ≥ 100 mg/mL (~716.23 mM)

Solubility in Formulation 1: ≥ 3.5 mg/mL (25.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 3.5 mg/mL (25.07 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 3.5 mg/mL (25.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 130 mg/mL (931.10 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)