Cysteamine

Absorption

Orally administered cysteamine is absorbed in the gastrointestinal tract and reaches its maximum plasma concentration in about 1.4 hours, with some variation according to the type of formulation (delayed versus immediate-release). One pharmacokinetic study of adults with Cystic Fibrosis revealed a Cmax of 2.86 mg/L.The maximum plasma concentration after administration of cysteamine eye drops is unknown, however, it is likely to be considerably lower than oral administration.
According to prescribing information, the AUC 0-12 h for the delayed-release oral tablets is 99.26 ± 44.2 μmol*h/L with a Cmax of 27.70 ± 14.99 μmol/L.
The AUC 0-12 for the immediate-release tablets is 192.00 ± 75.62 μmol*h/L with a Cmax of 37.72 ± 12.10 μmol/L.

Toxicity

Two cases of human overdoses with cysteamine are recorded in the literature, according to prescribing information. In one case, vomiting was immediate after the administration of cysteamine, and the patient did not experience other symptoms. A 200 to 250 mg/kg dose was accidentally ingested by a healthy 13-month-old child. Vomiting and dehydration followed. A full recovery was made after hospitalization and the replenishment of fluids.
There is no known antidote for an overdose with cysteamine. In the case of an overdose, provide supportive treatment, especially to the cardiovascular and respiratory systems. Hemodialysis may be useful in some cases due to the fact that cysteamine has poor plasma protein binding.

Description

2-AMINOETHANETHIOL is the chemical compound with the formula HSCH₂CH₂NH₂. It is the simplest stable aminothiol and a degradation product of the amino acid cysteine. It is often used as the hydrochloride salt, HSCH₂CH₂NH₃Cl. The comparatively high melting point of cysteamine (95-97 °C), indicates that exists in a salt form.

Chemical properties

2-AMINOETHANETHIOL is white powder

The Uses of Cysteamine

2-Aminoethanethiol is used in preparation method of fluorescence quenching array sensor based on cadmium telluride quantum dots and application in qualitative discrimination and quantitative analysis of organic acids.

The Uses of Cysteamine

antihyperlipidemic, HMGCoA reductase inhibitor

The Uses of Cysteamine

Scavenges benzyl and allyl halides and ketones.

The Uses of Cysteamine

Cysteamine is suitable for use:

• in the preparation of cysteamine modified gold nanoparticles (AuNP)
• in the fabrication of SU-8 microrods, where in, the amine group of cysteamine reacts with the unreacted epoxide rings present on the surface of the particles, thereby opening it and forming a covalent bond
• to enhance in vitro development of porcine oocytes matured and fertilized in vitro
• in a study to demonstrate the depletion effect of cysteamine on cystinotic leucocyte granular fractions of cystine by disulphide interchange
• as a radioprotector
• to administer subcutaneously in rats to study its blocking effect on somatostatin secretion without modifying the pancreatic insulin or glucagon content
• as a scavenger in electrophoretic gels (acetic acid/urea gels)

Indications

The bitartrate salt of cysteamine is used for the oral treatment of nephropathic cystinosis and cystinuria in adults and children ≥6 years old. The hydrochloride salt, used in eye drop preparations, is indicated for the treatment of corneal cystine crystal accumulation in patients with cystinosis.

Background

Cystinosis is a rare disease caused by mutations in the CTNS gene that encodes for cystinosin, a protein responsible for transporting cystine out of the cell lysosome. A defect in cystinosin function is followed by cystine accumulation throughout the body, especially the eyes and kidneys.
Several preparations of cysteamine exist for the treatment of cystinosis manifestations, some in capsule form, and others in ophthalmic solution form. In particular, cystine deposits on the eye can cause significant discomfort throughout the day and require frequent treatment with eye drops, typically every waking hour.
On August 25th 2020, the first ophthalmic solution for cystinosis requiring only 4 daily treatments was granted FDA approval. Cysteamine eye drops are a practical and effective option for those affected by ocular cystinosis. Marketed by Recordati Rare Diseases Inc., CYSTADROPS? reduce the burden of multiple frequent medications normally administered to those with cystinosis.

Definition

2-AMINOETHANETHIOL is an amine that consists of an ethane skeleton substituted with a thiol group at C-1 and an amino group at C-2.

Preparation

Cysteamine can also be prepared by the reaction of ethylenimine with hydrogen sulfide.
(NHCH₂CH₂) + H₂S → HSCH₂CH₂NH₂.

Reactions

2-AMINOETHANETHIOL is used as the hydrochloride salt, as it readily oxidizes to the corresponding disulfide, in the presence of air. The amine portion of the molecule serves as a catalyst for this reaction.
4 HSCH₂CH₂NH₂ + O₂ → 2 NH₂CH₂CH₂SSCH₂CH₂NH₂ + 2 H₂O.

Pharmaceutical Applications

Under the trade name Cystagon, cysteamine is used in the treatment of disorders of cystine excretion. Cysteamine cleaves the disulfide bond with cystine to produce molecules that can escape the metabolic defect in cystinosis and cystinuria.
It is also used for treatment of radiation sickness.
Cysteamine is used in the body to form the essential biochemical coenzyme A by combining with pantothenate and adenosine triphosphate.
In 2008, Raptor Pharmaceuticals started phase II clinical trials testing a delayed release (DR) preparation of cysteamine bitartrate for Huntington's disease. DR Cysteamine is also being investigated as a treatment for cystinosis, Batten disease, and non-alcoholic steatohepatitis.

Biochem/physiol Actions

Cysteamine (β-mercaptoethylamine) depletes cystine from patient′s cells and there by regulates renal glomerular function and increases growth in them. Therefore, cysteamine is considered to be a potential therapeutic for nephropathic cystinosis.

Pharmacokinetics

Cystine accumulation is the cause of organ damage in cystinosis. Cysteamine prevents the accumulation of cystine crystals in the body and is specifically prescribed to prevent kidney and eye damage. Cysteamine converts cystine into a form that may easily exit cells, preventing harmful accumulation.

Safety Profile

Poison by intravenous, subcutaneous, and intraperitoneal routesModerately toxic by ingestion. Experimental reproductive effects. Mutation data reported. When heated to decomposition it emits very toxic fumes of SO, and NOx,.

Metabolism

There is limited information in the literature regarding the metabolism of cysteamine. This drug undergoes significant first-pass metabolism.

Purification Methods

It is soluble in H2O giving an alkaline reaction, and it has a disagreeable odour. A likely impurity is the disulfide cystamine which is not soluble in alkaline solution. Under a N2 atmosphere dissolve it in EtOH, evaporate to dryness and wash the white residue with dry pet ether, then sublime it at 0.1mm and store it under N2 at 0-10o in the dark. Its HgCl2 (2:3) complex has m 181-182o (from H2O), and its picrate has m 125-126o. [Mills & Bogert J Am Chem Soc 57 2328 1935, 62 1173 1940, Baddiley & Thain J Chem Soc 800 1952, Shirley Preparation of Organic Intermediates (J. Wiley) Vol 3 189 1951, Barkowski & Hedberg J Am Chem Soc 109 6989 1987, Beilstein 4 IV 1570.]