Cysteamine is a chemical compound that can be biosynthesized in mammals, including humans, by the degradation of coenzyme A. The intermediate

pantetheine Pantetheine is the cysteamine amide structural analog, analog of pantothenic acid (vitamin B5). The dimer of this compound, pantethine is more commonly known, and is considered to be the most potent form of vitamin B5. Pantetheine is an intermedi ...

is broken down into cysteamine and

pantothenic acid Pantothenic acid, also called vitamin B5 is a water-soluble B vitamin and therefore an essential nutrient. All animals require pantothenic acid in order to synthesize coenzyme A (CoA) – essential for fatty acid metabolism – as well as to, i ...

. It is the biosynthetic precursor to the neurotransmitter

hypotaurine Hypotaurine is a sulfinic acid that is an intermediate in the biosynthesis of taurine. Like taurine, it also acts as an endogenous neurotransmitter via action on the glycine receptors. It is an osmolyte with antioxidant properties. Hypotaurine is ...

. It is a stable aminothiol, i.e., an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

containing both an

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...

and a

thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl gro ...

functional groups. Cysteamine is a white, water-soluble solid. It is often used as salts of the ammonium derivative SCH₂CH₂NH₃sup>+ including the hydrochloride, phosphocysteamine, and

bitartrate , Section2 = {{Chembox Properties , C=4 , H=5 , O=6 , Formula_Charge = − , ConjugateAcid = Tartaric acid , ConjugateBase = Tartrate Bitartrate is an anion which is the conjugate base of tartaric acid. It may also refer to any salt or ...

. As a medication, cysteamine, sold under the brand name Cystagon among others, is indicated to treat

cystinosis Cystinosis is a lysosomal storage disease characterized by the abnormal accumulation of cystine, the oxidized dimer of the amino acid cysteine. It is a genetic disorder that follows an autosomal recessive inheritance pattern. It is a rare autosom ...

Medical uses

Cysteamine is used to treat

. It is available by mouth (capsule and extended release capsule) and in

eye drop Eye drops or eyedrops are liquid drops applied directly to the surface of the eye usually in small amounts such as a single drop or a few drops. Eye drops usually contain saline to match the salinity of the eye. Drops containing only saline ...

s. When applied topically it can scavenge free radicals and lighten skin that's been darkened as a result of post-inflammatory hyperpigmentation, sun exposure and

Melasma Melasma (also known as chloasma faciei,James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . or the mask of pregnancy when present in pregnant women) is a tan or dark ...

. Tentative evidence suggests that it may be a more effective

depigmentation Depigmentation is the lightening of the skin or loss of pigment. Depigmentation of the skin can be caused by a number of local and systemic conditions. The pigment loss can be partial (injury to the skin) or complete (caused by vitiligo). It can be ...

agent than

hydroquinone Hydroquinone, also known as benzene-1,4-diol or quinol, is an aromatic organic compound that is a type of phenol, a derivative of benzene, having the chemical formula C6H4(OH)2. It has two hydroxyl groups bonded to a benzene ring in a ''para'' ...

retinoid The retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it. Retinoids have found use in medicine where they regulate epithelial cell growth. Retinoids have many important functions throughout t ...

s and topical

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...

s in individuals with chronic skin discoloration. Topical application of cysteamine cream has also demonstrated similar efficacy to

intradermal Intradermal injection, often abbreviated ID, is a shallow or superficial injection of a substance into the dermis, which is located between the epidermis and the hypodermis. For certain substances, administration via an ID route can result in a ...

tranexamic acid Tranexamic acid (TXA) is a medication used to treat or prevent excessive blood loss from major trauma, postpartum bleeding, surgery, tooth removal, nosebleeds, and heavy menstruation. It is also used for hereditary angioedema. It is taken eith ...

injections for the treatment of Melasma but with much fewer adverse effects.

Adverse effects

Topical use

The most important adverse effect related to topical use might be skin irritation. However it's significantly better tolerated than alternative skin lightening treatments with similar efficacy.

Oral use

The label for oral formulations of cysteamine carry warnings about symptoms similar to Ehlers-Danlos syndrome, severe skin rashes, ulcers or bleeding in the stomach and intestines, central nervous symptoms including seizures, lethargy, somnolence, depression, and encephalopathy, low white blood cell levels,

elevated alkaline phosphatase Elevated alkaline phosphatase occurs when levels of alkaline phosphatase (ALP) exceed the reference range. This group of enzymes has a low substrate specificity and catalyzes the hydrolysis of phosphate esters in a basic environment. The major fu ...

, and idiopathic intracranial hypertension that can cause headache, tinnitus, dizziness, nausea, double or blurry vision, loss of vision, and pain behind the eye or pain with eye movement. The main side effects are Ehlers-Danlos syndrome, severe skin rashes, ulcers or bleeding in the stomach and intestines, central nervous symptoms, low white blood cell levels,

, and idiopathic intracranial hypertension (IIH). IIH can cause headache, ringing in the ears, dizziness, nausea, blurry vision, loss of vision, and pain behind the eye or with eye movement. Additional adverse effects of oral cysteamine include bad breath, skin odor, vomiting, nausea, stomach pain, diarrhea, and loss of appetite. The drug is in pregnancy category C; the risks of cysteamine to a fetus are not known but it harms babies in animal models at doses less than those given to people. For eye drops, the most common adverse effects are sensitivity to light, redness, and eye pain, headache, and visual field defects.

Interactions

There are no drug interactions for normal capsules or eye drops, but the extended release capsules should not be taken with drugs that affect stomach acid like

proton pump inhibitors Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump. They are the most potent inhibitors ...

or with alcohol, as they can cause the drug to be released too quickly. It doesn't inhibit any

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

enzymes.

Pharmacology

People with

lack a functioning transporter (cystinosin) which transports cystine from the lysosome to the cytosol. This ultimately leads to buildup of

cystine Cystine is the oxidized derivative of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a me ...

in lysosomes, where it crystallizes and damages cells. Cysteamine enters lysosomes and converts cystine into

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

and cysteine-cysteamine mixed disulfide, both of which can exit the lysosome.

Biological function

Cysteamine also promotes the transport of L-cysteine into cells, that can be further used to synthesize glutathione, which is one of the most potent intracellular antioxidants. Cysteamine is used as a drug for the treatment of

; it removes

that builds up in cells of people with the disease.

History

First evidence regarding the therapeutic effect of cysteamine on cystinosis dates back to 1950s. Cysteamine was first approved as a drug for cystinosis in the US in 1994. An extended release form was approved in 2013.

Society and culture

It is approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) and the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA). In 2013, the regular capsule of cysteamine cost about $8,000 per year; the extended release form that was introduced that year was priced at $250,000 per year.

Research

It was studied in ''in vitro'' and animal models for

radiation protection Radiation protection, also known as radiological protection, is defined by the International Atomic Energy Agency (IAEA) as "The protection of people from harmful effects of exposure to ionizing radiation, and the means for achieving this". Expos ...

in the 1950s, and in similar models from the 1970s onwards for

sickle cell anemia Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...

, effects on growth, its ability to modulate the immune system, and as a possible inhibitor of HIV. In the 1970s it was tested in clinical trials for

Paracetamol toxicity Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. These include f ...

which it failed, and in clinical trials for

systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...

in the 1990s and early 2000s, which it also failed. Clinical trials in

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...

were begun in the 1990s and were ongoing as of 2015. , it was in clinical trials for

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

, radiation sickness, neurodegenerative disorders, neuropsychiatric disorders, and cancer treatment. It has been studied in clinical trials for pediatric

nonalcoholic fatty liver disease Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic ...

References

External links

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