S-Carboxymethyl-L-Cysteine

Absorption

Carbocisteine is rapidly absorbed in the gastrointestinal tract when taken orally with peak serum concentrations achieved within 1 to 1.7 hours.

Toxicity

The oral LD50 of carbocisteine in rats is >15000 mg/kg. An overdose with carbocisteine is likely to result in gastrointestinal discomfort with nausea and vomiting.

Chemical properties

white to slightly off-white amorphous powder

Originator

Rhinathiol,Kramer,Switz.

The Uses of S-Carboxymethyl-L-Cysteine

Carbocisteine is a mucolytic agent used in the treatment of respiratory disorders ranging from the influenza virus infection to chronic obstructive pulmonary disease (COPD).

The Uses of S-Carboxymethyl-L-Cysteine

Labeled Carbocisteine, intended for use as an internal standard for the quantification of Carbocisteine by GC- or LC-mass spectrometry.

The Uses of S-Carboxymethyl-L-Cysteine

carbocysteine is an amino acid. It can be used to help control sebum production.

Background

Dyspnea and cough are common symptoms of chronic obstructive pulmonary disease (COPD) and other respiratory conditions characterized by increased mucus production. Individuals with COPD have a greater risk of pulmonary infection due to the growth and accumulation of viruses and bacteria in thick bronchial mucus. Carbocisteine is a mucolytic drug that alleviates respiratory symptoms and infections by reducing the viscosity of mucus, allowing it to be expelled.
Several licenses for this drug were withdrawn following serious and fatal paradoxical effects after carbocisteine therapy in children; respiratory dress, dyspnea, and cough aggravation were reported by physicians in France and Italy. Carbocisteine is currently not FDA or Health Canada approved, but is approved for use in Asia, Europe, and South America.

Indications

Carbocisteine is indicated over the counter and in prescription formulas to clear airway secretions in conditions associated with increased mucus.

What are the applications of Application

S-Carboxymethyl-L-cysteine is a mucolytic agent

Definition

ChEBI: S-carboxymethyl-L-cysteine is an L-cysteine thioether that is L-cysteine in which the hydrogen of the thiol group has been replaced by a carboxymethyl group. It has a role as a mucolytic. It is a L-cysteine thioether and a non-proteinogenic L-alpha-amino acid. It is a conjugate acid of a S-carboxylatomethyl-L-cysteine(1-).

Manufacturing Process

There were placed 120g of L-cysteine (0.5 mol) in a 2 liter three-necked flask equipped with a stirrer thermometer and methanol/dry ice cooling and 1.5 liters of liquid ammonia were allowed to enter at -40°C. Then there were added under continuous cooling 50 g (2.17 mols) of sodium metal in portions of 1 to 2 g during the course of one hour. The end of the reaction was recognized by the continuation of the blue color. After the end of the reaction the excess sodium was destroyed by the addition of ammonium chloride and the ammonia vaporized at normal pressure. The residue was taken up in 500 ml of water and concentrated in a vacuum to 200 ml in order to remove residual ammonia, and again treated with 300 ml of water. The entire operations were carried out under a nitrogen atmosphere.
The aqueous solution of the disodium salt of L-cysteine obtained is then reacted at 20°C to 30°C under a nitrogen atmosphere in the course of 30 minutes with stirring with a solution of 104 g of chloroacetic acid (1.1 mols) and 4 g of sodium pyrosulfite in 200 ml of water. It is also allowed to post react for 15 minutes at 20°C, the solution clarified over activated carbon and the filtrate treated with 90 ml of concentrated hydrochloric acid to a pH of 2.5.
Thereby the S-carboxymethyl-L-cysteine precipitates out in crystalline form. The product is filtered off with suction, well stirred in 500 ml of water, again filtered with suction and dried in a vacuum at 70°C. The yield is 92% based on L-cysteine.

brand name

Loviscol (Wyeth-Ayerst); Mucofan (Wyeth-Ayerst).

Therapeutic Function

Mucolytic, Expectorant, Nasal antiinfective

Biochem/physiol Actions

S-Carboxymethyl-L-cysteine is studied as a small molecule mucoactive drug in vivo. These studies include analyzing the oxidative metabolism of S-carboxymethyl-L-cysteine by enzymes such as phenylalanine monooxygenase(s).

Pharmacokinetics

Due to its mucolytic effects, carbocisteine significantly reduces sputum viscosity, cough, dyspnea and fatigue. Additionally, it prevents pulmonary infections by decreasing accumulated mucus in the respiratory tract; this is especially beneficial in preventing exacerbations of COPD caused by bacteria and viruses. It has in-vitro anti-inflammatory activity with some demonstrated action against free radicals.

Safety Profile

contact. A riot control agent. When heated

Metabolism

Metabolic pathways for carbocisteine include acetylation, decarboxylation, and sulfoxidation, leading to the formation of pharmacologically inactive carbocisteine derivatives. Significant variability exists in metabolism due to genetic polymorphism in sulfoxidation capacity. Two cytosolic enzymes are responsible for the metabolism of carbocisteine: cysteine dioxygenase and phenylalanine 4-hydroxylase. Reduced metabolism can cause increased exposure to carbocisteine, explaining variable clinical response between patients who may polymorphisms affecting the enzymes responsible for carbocisteine metabolism. It is generally accepted that sulfodixation is the main metabolic pathway of carbocisteine, however, one group of researchers found a novel urinary metabolite, S-(carboxymethylthio)-L-cysteine (CMTC). No cysteinyl sulfoxide metabolites were found in the urine of patients taking carbocisteine in this study.