Anetholtrithion does not have a well-defined single molecular target. It acts as a choleretic, stimulating bile production and secretion. It is also used to increase salivary secretion in patients with xerostomia. Its mechanism may involve the stimulation of the autonomic nervous system.

Enhancing glutathione levels and phase II detoxifying enzymes, amethyletherthione is a choleretic (a medication that stimulates bile production) and slow-release donor of H2S that protects the liver. By accelerating the rate at which carcinogens in the liver and colon are detoxified, anetholetrithione is a potentially useful chemopreventive drug for lung cancer that also has chemopreventive effects on other target organs. Following cerebral ischemia, anethole trithione can preserve the blood-brain barrier's integrity [2].
In vitro, anetholtrithion has been studied for its effects on bile acid synthesis and secretion. It may also have antioxidant properties due to its sulfur-containing structure. Its effects are measured in biochemical and cell-based assays.

Rat submandibular gland salivary production is increased by electrical stimulation of parasympathetic neurons and injection of pilocarpine when treated chronically with anetholetrithione. Increased muscarinic acetylcholine receptors occur along with increased salivary secretion [3].
In vivo, anetholtrithion is used as a choleretic to treat biliary tract disorders and as a sialogogue to treat dry mouth. It is administered orally. It has been used clinically in some countries.

Anetholtrithion does not have a specific enzyme or receptor binding assay in a pharmacological context. Its choleretic activity can be assessed by measuring bile flow in animal models. Its effects on salivary secretion can be measured in vivo.

In vitro cellular assays for anetholtrithion are not commonly performed, as its primary effects are on bile and saliva secretion. Its potential antioxidant activity can be measured using cell-free assays such as DPPH radical scavenging.

In vivo animal experiments for anetholtrithion are conducted to study its choleretic and sialogogue effects. Bile duct-cannulated animals are used to measure bile flow after drug administration. Salivary secretion is measured in animal models of xerostomia.

Absorption, Distribution and Excretion
While anethole trithione (ATT) exhibits high lipophilicity (log P = 3.8) and high intestinal permeability, its water solubility is extremely low (0.38 ug/ml). This low solubility limits the solubility and bioavailability of ATT. Nevertheless, in 22 healthy Chinese volunteers, after administration of ATT, the observed Cmax was approximately 0.98 ± 0.49 ng/mL, and the recorded Tmax was 2.2 ± 1.9 h. Although this drug has been studied and discussed since the 1980s, detailed pharmacokinetic information has not been readily available, and limited new pharmacokinetic data were only recently established (in 2007). However, the low absorption and bioavailability of anethole trithione indicate that any type of volume of distribution measurement may not be entirely accurate. Although this drug has been studied and discussed since the 1980s, detailed pharmacokinetic information has not been readily available, and limited new pharmacokinetic data were only recently (2007). Nevertheless, the estimated clearance of anethole trithione observed after oral administration of an aqueous suspension to rats was approximately 113.20 ± 52.37 L/h/kg. Metabolites/Metabolites Anethole trithione (ATT) is rapidly metabolized to 4-hydroxyanisole trithione via O-demethylation. This metabolite exhibits pharmacological activity similar to its parent, ATT. Some studies have proposed that this metabolism occurs in hepatic microsomes, but this hypothesis and the specific hepatic cytochrome P450 isoenzymes involved in this metabolism have not been formally elucidated.

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Biological Half-Life
Although this drug was studied and discussed as early as the 1980s, detailed pharmacokinetic information was not readily available, and limited new pharmacokinetic data were only recently (2007). Therefore, after administration of anethole trithione to 22 healthy Chinese volunteers, the observed half-life was approximately 3.78 ± 2.12 hours.

Anetholtrithion has been used clinically and has characterized pharmacokinetic properties. It is absorbed after oral administration and is metabolized in the liver. Its half-life and excretion have been studied. It is typically stored as a solid.

Protein Binding
Although the drug was studied and discussed as early as the 1980s, detailed pharmacokinetic information about it was not readily available, and limited new pharmacokinetic data for the drug were only recently determined (most recently in 2007).
Anetholtrithion is generally well-tolerated. Common side effects may include gastrointestinal disturbances. It is contraindicated in patients with biliary obstruction. Its safety profile has been established in clinical use.

[1]. Enhancement of salivary secretion and neuropeptide (substance P, alpha-calcitonin gene-related peptide) levels in saliva by chronic anethole trithione treatment. J Pharm Pharmacol. 2001 Dec;53(12):1697-702.

[2]. Synthesis, Characterization, and In Vivo Evaluation of Desmethyl Anethole Trithione Phosphate Prodrug for Ameliorating Cerebral Ischemia-Reperfusion Injury in Rats. ACS Omega. 2020 Feb 24;5(9):4595-4602.

[3]. Chronic anethole trithione treatment enhances the salivary secretion and increases the muscarinic acetylcholine receptors in the rat submaxillary gland. Arch Int Pharmacodyn Ther. 1984 Oct;271(2):206-12.

Pharmacodynamics
Anethole trithione (ATT) exhibits high lipophilicity (log P = 3.8) but extremely low water solubility (0.38 μg/mL), limiting its dissolution and absorption. Furthermore, ATT is rapidly metabolized to 4-hydroxyanisole trithione (ATX, with similar pharmacological activity to ATT) via O-demethylation. Therefore, ATT plasma concentrations are typically low, resulting in limited oral bioavailability. Given these pharmacodynamic characteristics, researchers continue to focus on developing carriers that can improve the in vivo bioavailability of ATT.
Anetholtrithion is a drug used as a choleretic and for the treatment of xerostomia. It is also known as anethole trithione and is marketed under brand names such as Felviten and Heporal. It is approved for use in some countries.

C10H8OS3

240.35

239.973

532-11-6

Anethole;104-46-1

2194

Yellow to orange solid powder

1.4±0.1 g/cm3

398.1±52.0 °C at 760 mmHg

23 C

194.6±30.7 °C

0.0±0.9 mmHg at 25°C

1.732

3.39

0

4

2

14

254

0

KYLIZBIRMBGUOP-UHFFFAOYSA-N

InChI=1S/C10H8OS3/c1-11-8-4-2-7(3-5-8)9-6-10(12)14-13-9/h2-6H,1H3

5-(4-methoxyphenyl)dithiole-3-thione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~12.5 mg/mL (~52.01 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 25.0 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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 (Please use freshly prepared in vivo formulations for optimal results.)