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].

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].

Absorption, Distribution and Excretion
Although anethole trithione (ATT) has a high lipophilicity (log P = 3.8) and a high intestinal permeability, it has an extremely low water solubility (0.38 ug/ml). This low solubility limits ATT dissolution and bioavailability. Regardless, after ATT was administered to twenty-two healthy Chinese volunteers, the Cmax observed was about 0.98 +/- 0.49 ng/mL and the recorded Tmax was 2.2 +/- 1.9 h.
Despite the medication being studied and discussed as early as the 1980s, detailed pharmacokinetic information about it is not readily accessible and limited new pharmacokinetic data has only been determined for the drug for the first time only very recently (as recently as 2007).
Despite the medication being studied and discussed as early as the 1980s, detailed pharmacokinetic information about it is not readily accessible and limited new pharmacokinetic data has only been determined for the drug for the first time only very recently (as recently as 2007). Nevertheless, the poor absorption and bioavailability of anethole trithione suggests any kind of volume of distribution measurement may not be entirely accurate.
Despite the medication being studied and discussed as early as the 1980s, detailed pharmacokinetic information about it is not readily accessible and limited new pharmacokinetic data has only been determined for the drug for the first time only very recently (as recently as 2007). Regardless, data about the estimated clearance of anethole trithione in the rat model after administration of anethole trithione oral aqueous suspension was observed to be approximately 113.20 +/- 52.37 L/h/kg.

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Metabolism / Metabolites
Anethole trithione (ATT) is metabolized rapidly into 4-hydroxy-anethole trithione via O-demethylation. This metabolite demonstrates similar pharmacological activities to its parent, ATT. It is proposed that such metabolism occurs in liver microsomes, although neither this proposal or by what specific hepatic cytochrome P450 isoform(s) are involved in such metabolism has been formally elucidated.

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Biological Half-Life
Despite the medication being studied and discussed as early as the 1980s, detailed pharmacokinetic information about it is not readily accessible and limited new pharmacokinetic data has only been determined for the drug for the first time only very recently (as recently as 2007). Consequently, after anethole trithione was administered to twenty-two healthy Chinese volunteers, the half-life observed was about 3.78 +/- 2.12 hours.

Protein Binding
Despite the medication being studied and discussed as early as the 1980s, detailed pharmacokinetic information about it is not readily accessible and limited new pharmacokinetic data has only been determined for the drug for the first time only very recently (as recently as 2007).

[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
Anethol trithione (ATT) possesses a high lipophilicity (log P = 3.8) but an extremely low water solubility (0.38 ug/mL), which limits its dissolution and absorption. Furthermore, ATT is quickly metabolized into 4-hydroxy-anethole trithione (ATX, which demonstrates a similar pharmacological activity to ATT) by way of O-demethylation. As a consequence, the plasma concentration of ATT is usually fairly low, resulting in a limited oral bioavailability as well. Given this pharmacodynamic profile, there is continued interest and study in developing vehicles with which ATT can be administered in larger availabilities into the body.

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.)