Cycloserin

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Listed in ZINC15

Polyketides [PK] -> Non-ribosomal peptide/polyketide hybrids [PK14]

Polyketides [PK] -> Non-ribosomal peptide/polyketide hybrids [PK14]

CRYSTALS

WHITE TO PALE YELLOW, CRYSTALLINE POWDER

Soluble

SOL IN WATER; SLIGHTLY SOL IN METHANOL, PROPYLENE GLYCOL

8.77e+02 g/L

Breast Feeding; Lactation; Anti-infective Agents; Antibiotics, Antitubercular

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Antituberculosis medicines

155-156 °C (decomposes)

147 °C

This chemical does not meet GHS hazard criteria for 80% (4 of 5) of all reports.

Warning

H302 (20%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 5 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

ISONIAZID SHOULD NOT BE GIVEN WITH CYCLOSERINE BECAUSE OF POSSIBLE ADDITIVE CENTRAL NERVOUS SYSTEM TOXICITY.

/Cycloserine/ may increase the risk of seizures, especially in chronic alcohol abuse; patients should be advised to avoid concurrent use.

Concurrent use /with isoniazid/ may result in increased incidence of CNS effects such as dizziness or drowsiness; dosage adjustments may be necessary, and patients should be monitored for signs of CNS toxicity.

Cycloserine may cause anemia or peripheral neuritis by acting as a pyridoxine antagonist or increasing renal excretion of pyridoxine; requirements for pyridoxine may be increased in patients receiving cycloserine.

Cycloserine is reported to be associated with a low rate of serum aminotransferase elevations that are usually transient and asymptomatic and do not require dose modification. Cycloserine is usually used in combination with agents that are more clearly linked to liver test abnormalities, and it generally plays little or no role in these abnormalities. Cycloserine has not been definitely linked to instances of clinically apparent liver injury, but is often used with agents that are known hepatotoxins and its possible contribution cannot always be excluded.

Limited information is available on acute overdosage of cycloserine. Symptoms of acute toxicity generally involve the CNS and include headache, vertigo, confusion, drowsiness, hyperirritability, paresthesias, dysarthria, and psychosis. Paresis, seizure, and coma may occur with large cycloserine overdosages; alcohol ingestion may increase the risk of seizures.

... Caused ill-defined visual disturbances in addition to drowsiness and mental confusion. ... Five out of 414 patients had eye symptoms consisting of flickering or feeling of pressure ... One instance of flickering vision and one of conjunctivitis /was reported/ among twenty-seven patients under treatment.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Cycloserine

Ambiguous-DILI-concern

3

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

D-CYCLOSERINE, 200 MG/KG IP INCR B-ALANINE & D-B-AMINOISOBUTYRIC ACID IN RAT LIVER & INHIBITED D-B-AMINOISOBUTYRIC ACID PYRUVATE & B-ALANINE-A-KETOGLUTARATE AMINOTRANSFERASES.

Cycloserine was not mutagenic in the Ames microbial mutagen test or the unscheduled DNA repair test. Studies have not been performed to date to evaluate the carcinogenic potential of cycloserine.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

J04AB01

Cycloserine, a broad-spectrum antibiotic, may be bactericidal or bacteriostatic, depending on its concentration at the site of infection and the susceptibility of the organism. Cycloserine works by blocking the formation of these peptidoglycans. By doing this the walls of the bacteria become weak and it results in the death of the bacteria

Cycloserine is an analog of the amino acid D-alanine. It interferes with an early step in bacterial cell wall synthesis in the cytoplasm by competitive inhibition of two enzymes, L-alanine racemase, which forms D-alanine from L-alanine, and D-alanylalanine synthetase, which incorporates D-alanine into the pentapeptide necessary for peptidoglycan formation and bacterial cell wall synthesis.

EXCRETION OF B-ALANINE & D-BETA-AMINOISOBUTYRIC ACID WAS INCR IN PT WITH TUBERCULOSIS RECEIVING CLINICAL DOSES OF D-CYCLOSERINE.

Cycloserine is inhibitory for Mycobacterium tuberculosis in concentrations of 5 to 20 ug/ml in vitro. There is no cross-resistance between cycloserine and other tuberculostatic agents. While the antibiotic is effective in experimental infections caused by other microorganisms, studies in vitro reveal no suppression of growth in cultures made in conventional media, which contain D-alanine; this amino acid blocks the antibacterial activity of cycloserine. ... Cycloserine inhibits reactions in which D-alanine is involved in bacterial cell-wall synthesis. The use of media free of D-alanine reveals that the antibiotic inhibits the growth in vitro of enterococci, E. coli, Staph. aureus, Nocardia species, and Chlamydia.

Half-life in patients with normal renal function is 10 hours, and is prolonged in patients with impaired renal function.

Normal renal function - 10 hours. Impaired renal function - prolonged.

Substances capable of killing agents causing urinary tract infections or of preventing them from spreading.

Substances obtained from various species of microorganisms that are, alone or in combination with other agents, of use in treating various forms of tuberculosis; most of these agents are merely bacteriostatic, induce resistance in the organisms, and may be toxic.

Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033)

Rapidly and almost completely absorbed (70 to 90%) from the gastrointestinal tract following oral administration.

VALUE OF CYCLOSERINE IS ENHANCED BY FACT THAT IT DIFFUSES INTO CELLS & CROSSES BLOOD-BRAIN BARRIER, EVEN IN ABSENCE OF DISEASE.

When given orally, 70% to 90% of cycloserine is rapidly absorbed. Peak concentrations in plasma are reached 3 to 4 hours after a single dose and are in the range of 20 to 35 ug/ml in children who receive 20 mg/kg; only small quantities are present after 12 hours.

Cycloserine is distributed throughout body fluids and tissues. There is no appreciable blood-brain barrier to the drug, and CSF concentrations in all patients are approximately the same as those in plasma. About 50% of a parenteral dose of cycloserine is excreted unchanged in the urine in the first 12 hours; a total of 65% is recoverable in the active form over a period of 72 hours.

In the treatment of nocardiosis, sulfonamides have been used with cycloserine.

MEDICATION

Originally isolated from many Streptomyces species...now produced only synthetically.

AGRICULTURAL FUNGICIDE