Find, compare & contact
Anethole trithione API Manufacturers & Suppliers

General Description:

Anethole trithione, identified by CAS number 532-11-6, is a notable compound with significant therapeutic applications. Anethole trithione (ATT) appears to have a broad range of unique functions, from increasing salivary secretion to help treat xerostomia , to demonstrating an ability to inhibit carcinogenesis by increasing the activity of electrophile detoxification enzymes , and even being used as an adjunctive therapy for cholecystitis, gallstone, indigestion, and acute/chronic hepatitis and is marketed in certain countries like France, Germany, and China . Unfortunately, many of the specific mechanisms of action to these activities have yet to be formally elucidated, which means that while studies are ongoing, ATT itself is not necessarily formally indicated for many of these aforementioned functions at this time and is only used in limited regions around the world.

Indications:

This drug is primarily indicated for: The most typical uses for which anethol trithione is currently indicated for includes increasing salivary secretion in patients experiencing dry mouth or being used as an adjunctive therapy for cholecystitis, gallstone, indigestion, and acute/chronic hepatitis . In addition, although some studies have suggested that anethol trithione also possesses a certain capacity to inhibit tumorigenesis as a potential cancer therapy medication, the specific mechanism of action for this effect remains to be elucidated with certain national cancer institutes listing the agent as 'a substance that is being studied in the treatment of cancer' . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Anethole trithione undergoes metabolic processing primarily in: 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 . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Anethole trithione are crucial for its therapeutic efficacy: 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 . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Anethole trithione is an important consideration for its dosing schedule: 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 . This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Anethole trithione exhibits a strong affinity for binding with plasma proteins: 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) . This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Anethole trithione from the body primarily occurs through: 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) . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Anethole trithione is distributed throughout the body with a volume of distribution of: 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. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Anethole trithione is a critical factor in determining its safe and effective dosage: 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 . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Anethole trithione exerts its therapeutic effects through: 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 . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Anethole trithione functions by: Epidemiological studies demonstrate that the prevalence of xerostomia and salivary gland hypofunction (SGH) rises with age, and is largely associated with medications and health . In particular, anethole trithione (ATT) is believed to cause an increase in salivary secretion by upregulating the number of muscarinic receptor (whose stimulation is known to increase salivary secretion) sites on the salivary acinar cells . Moreover, the combination use of ATT and pilocarpine is also thought to be effective in a synergistic manner - as ATT increases the number of cell surface receptors on salivary acinar cells, the pilocarpine, which is a parasympathetic agent, stimulates the newly formed receptors . In addition, studies have also shown that the administration of ATT can also enhance the upregulation and release of substance P and alpha-calcitonin gene-related peptide . As receptors for peptides like alpha-calcitonin gene-related peptide are found throughout the body, the increase in these such proteins may modulate a variety of physiological functions in various body systems, even in the gastrointestinal or salivary actions . Regardless, it has been shown that the use of ATT in patients can cause an increase in salivary flow rate in patients with xerostomia caused by senile hypofunction, medication side effects, and oral cancer therapy and has been indicated for use in treating xerostomia associated with conditions like Sjogren's syndrome . Nevertheless, there exist also studies that suggest ATT is generally only effective in managing the symptoms of mild salivary gland hypofunction but is not particularly useful for treating severe salivary gland hypofunction or severe cases of Sjogren's syndrome . ATT is also used as an adjunctive therapy for cholecystitis, gallstone, indigestion, and acute/chronic hepatitis in certain countries like France, Germany, and China . With regards to this particular indication, it is believed that ATT can facilitate raises in the level of glutathione in the liver, and raises in the activity of glutamylcysteine synthetase, glutathione reductase, and glutathione S transferase . All of these effects are consequently intimately involved in the cellular antioxidant activity of glutathione where glutamylcysteine synthetase is the first enzyme involved in the cellular glutathione biosynthesis pathway; where glutathione reductase is necessary for catalyzing the reduction of pathway intermediates to glutathione; and glutathione S transferase catalyze the conjugation of the reduced form of glutathione to xenobiotic substrates for the purpose of detoxification . Finally, glutathione itself is an important antioxidant found in plants, animals, fungi, and some bacteria where it assists in preventing damage to cellular components caused by reactive oxygen species, free radicals, etc . Taken altogether, these various actions are suitable for treating cholecystitis, gall stones, indigestion, and may be used in the assisting treatment of acute and chronic hepatosis. Although the specific mechanism of action for which ATT is seemingly capable of inhibiting tumorigenesis to a certain degree remains to be elucidated, some potential plausible mechanisms have been discussed. One such potential mechanism suggests that ATT has the capability to alter the metabolism of carcinogens by increasing the rate of detoxification of carcinogens in target organs like the liver and colon, thereby decreasing the generation of carcinogen metabolites and reducing parent-carcinogen induced carcinogenesis by way of those agents . And finally, a second potential mechanism proposes that ATT can strikingly increase the antioxidant activities of colonic and liver GST, NAD(P)H:QR, and UDP-GT, therefore eliciting a chemoprotective action . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Anethole trithione belongs to the class of organic compounds known as anisoles. These are organic compounds containing a methoxybenzene or a derivative thereof, classified under the direct parent group Anisoles. This compound is a part of the Organic compounds, falling under the Benzenoids superclass, and categorized within the Phenol ethers class, specifically within the Anisoles subclass.

Categories:

Anethole trithione is categorized under the following therapeutic classes: Alimentary Tract and Metabolism, Anisoles, Benzene Derivatives, EENT Drugs, Miscellaneous, Ethers, Gastrointestinal Agents, Methyl Ethers, Phenols, Phenyl Ethers, Sialogogues, Sulfur Compounds, Thiones, Various Alimentary Tract and Metabolism Products. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.