Cycloserine side effects

Antituberculin Agents. Rifampin [13292-46-17, a semisynthetic derivative of rifamycin SV, is a most valuable dmg for treatment of tuberculosis, an infection caused by mycobacteria, leprosy, and an expanding range of other infections (23). Cycloserine [64-41-7] has been used to a limited extent for treatment of tuberculosis as a reserve dmg. Although cycloserine inhibits bacteria by interfering with their cell wall biosynthesis, it has toxic side effects in humans in the form of neurotoxicity. Capreomycin [11003-38-6] and to a much lesser extent viomycin [32988-50-4] both of which are peptides, have also been used for treatment of this disease. 

Neurological symptoms, which tend to appear in the first week of therapy, consist of dizziness, confusion, irritability, psychotic behavioral changes, and even suicidal ideation. Cycloserine is contraindicated in patients with underlying psychiatric and seizure disorders. Other side effects include occasional peripheral neuropathy and low magnesium levels. 

Side effects typically effect the CNS, appearing within 2 weeks of therapy and disappearing after drug withdrawal. They include somnolence, headache, tremor, dysarthria, vertigo, confusion, nervousness, irritability, psychotic states, paranoid reactions, catatonic reactions, twitching, ankle clonus, hyperreflexia, visual disturbances, paresis, and seizures. Large doses or concomitant ingestion of alcohol increases the risk of seizures. Cycloserine is contraindicated in individuals with a history of epilepsy and should be used with caution in individuals with a history of depression. 

Because human cells lack cell walls, they are generally unaffected by inhibitors of cell wall synthesis. This explains why penicillins and cephalosporins have few side effects. Vancomycin and D-cycloserine are quite toxic however, which suggests that these agents affect other processes in human cells. 

Mattila MJ, Nieminen E, Tiitinen H. Serum levels, urinary excretion, and side-effects of cycloserine in the presence of isoniazid and p-aminosalicylic acid. Scand J Respir Dis (1969) 50, 291-300. 

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