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
A study of choline pharmacokinetics was undertaken in four patients receiving long-term total parenteral nutrition. On consecutive days, 7, 14, 28, and 56 mmol choline chloride were intravenously infused over a 12-hour period in each subject. The choline concentration was determined in plasma at baseline, 1/4, 1, 3, 6, and 12 hours, and 3 and 12 hours after the infusion ended, and in daily 24-hour urine collections. Analysis of variance showed the data fit a two-compartment model in which elimination from the central compartment was saturable significantly better than a one-compartment model in all four subjects (p < 10-8 in all cases), and significantly better than a nonsaturating model in three of the four subjects (p = 1.0 x 10-9, 7.5 x 10-6, 9.4 x 10-11, respectively). The model allowed estimates of the rate constant for choline elimination at ambient levels, first-order rate constants for transfer between central and peripheral compartments, the dissociation constant for the saturable elimination process, the apparent volume of distribution in the central compartment, the steady-state volume of distribution, and the quantities of choline in the central compartment and in the readily exchangeable pool.
Choline chloride, a strong base, was surprisingly well absorbed at pH 7, but absorption was less at lower ph values.
Choline is absorbed from diet as such or as lecithin. Latter is hydrolyzed by intestinal mucosa to glycerophosphoryl choline, which either passes to liver to liberate choline or to peripheral tissues via intestinal lymphatics. /Choline/
Choline chloride (1-2 g, 4 times daily, increasing every 2 days, reaching max of 2-5 g 4 times daily, orally) dose-dependently incr serum choline levels in patients with Huntington's Disease, & incr cerebrospinal fluid choline levels not related to serum levels.
For more Absorption, Distribution and Excretion (Complete) data for CHOLINE CHLORIDE (11 total), please visit the HSDB record page.

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Metabolism / Metabolites
Free choline is not fully absorbed, especially after large doses, & intestinal bacteria metabolize choline to trimethylamine. /Choline/
/The/ ability to form choline /de novo via the methylation of phosphatidylethanolamine using S-adenosylmethionine as the methyl donor, mostly in the liver,/ means that some of the demand for choline can ... be met using methyl groups derived from 1-carbon metabolism (via methyl-folate and methionine). Several vitamins (folate, vitamin B12, vitamin B6, and riboflavin) and the amino acid methionine interact with choline in 1-carbon metabolism ... Methionine, methyl-tetrahydrofolate (THF), and choline can be fungible sources of methyl groups. /Choline/
Before choline can be absorbed in the gut, some is metabolized by bacteria to form betaine and methylamines (which are not methyl donors) ... Although some free choline is excreted with urine, most is oxidized in the kidney to form betaine ... /Choline/
Acetylcholine is one of the most important neurotransmitters used by neurons in the memory centers of the brain (hippocampus and septum). Choline accelerates the synth and release of acetylcholine in nerve cells. Choline used by brain neurons is largely derived from membrane lecithin /(phosphatidylcholine)/, or from dietary intake of choline and lecithin ... Choline derived from lecithin may be especially important when extracellular choline is in short supply, as might be expected to occur in advanced age because of decr brain choline uptake ... /Choline/
For more Metabolism/Metabolites (Complete) data for CHOLINE CHLORIDE (6 total), please visit the HSDB record page.

Maximum Drug Dose
The tolerable upper limit for choline has been set at 3 g/day.
Coates, P.M., Blackman, M.R., Cragg, G.M., Levine, M., Moss, J., White, J.D. (Ed), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, NY, p. 109 (2005)

The Tolerable Upper Intake Level (UL) for adults is 3.5 g/day.

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Interactions
Repeated admin of choline chloride to female rats incr liver necrosis caused by carbon tetrachloride. LEDDA GM ET AL; RASS MED SARDA 80(4) 215 (1977)

Lithium admin potentiates 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 appears as white crystals. Practically neutral aqueous solution. (NTP, 1992)
Choline chloride is a quaternary ammonium salt with choline cation and chloride anion. It has a role as an animal growth promotant. It is a chloride salt and a quaternary ammonium salt. It contains a choline.
A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.

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Mechanism of Action
Choline has several roles in body. It is an important component of phospholipids, affects mobilization of fat from liver (lipotropic action), acts as methyl donor, & is essential for formation of neurotransmitter acetylcholine. /Choline/
Several mechanisms are suggested for the cancer-promoting effect of a choline-devoid diet. These incl incr cell proliferation related to regeneration after parenchymal cell death occurs in the choline deficient liver, hypomethylation of DNA (alters expression of genes), reactive oxygen species leakage from mitochondria with incr lipid peroxidation in liver, activation of protein kinase C signaling due to accumulation of diacylglycerol in liver, mutation of the fragile histidine triad (FHIT) gene, which is a tumor suppressor gene, and defective cell-suicide (apoptosis) mechanisms. Loss of phposphatidylethanolamine N-methyl-transferase (PEMT) function may also contribute to malignant transformation of hepatocytes. /Choline/
Acetylcholine is one of the most important neurotransmitters used by neurons in the memory centers of the brain (hippocampus and septum). Choline accelerates the synth and release of acetylcholine in nerve cells. /Choline/
Female Sprague-Dawley rats received approximately 300 mg/kg per day of choline chloride through their drinking water on days 11 of pregnancy through birth and the level of nerve growth factor (NGF) in the hippocampus and frontal cortex of their male offspring was measured at 20 and 90 days of age. Prenatal choline supplementation caused significant increases in hippocampal NGF levels at 20 and 90 days of age, while levels of NGF in the frontal cortex were elevated in choline-supplemented rats at 20 days of age, but not 90 days of age. These results suggest that increases in NGF levels during development or adulthood may be one mechanism underlying improvements in spatial and temporal memory of adult rats exposed to elevated levels of choline chloride perinatally.

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.)