Azotomycin—Toxicologic, biochemical and pharmacologic studies in mice

Metabolism and action of amino acid analog anti-cancer agents

“…Furthermore, e-asparaginase augments the toxicity of the latter regimen but not the former (Cooney et al, 1974b). Mice receiving single lethal doses of azotomycin (>400 mg/kg) exhibited ataxia and tonic-clonic convulsions from 4-24 hr after drug administration.…”

“…Azotomycin, a tripeptide containing two moles of DON, behaves as an effective prodrug which undergoes cleavage in vitro and in vivo to yield the proximate antimetabolite, DON (Cooney et al, 1974b). Since its toxicity has been reported more extensively than DON's, data on its deleterious effects will be substituted for--but should provisionally be viewed as equivalent to--those produced by DON (Cooney et al, 1974b).…”

“…Although L-asparagine has no known neurotransmitter function, it is possible that a significant diminution in its concentration would prevent normal neuronal protein synthesis. Brain, liver, intestine and spleen are the organs principally damaged by azotomycin (Cooney et al, 1974b). One salient manifestation of the drug's toxicity is a profuse diarrhea which begins about 18 hr after large single intravenous doses and persists until death.…”

“…Since its toxicity has been reported more extensively than DON's, data on its deleterious effects will be substituted for--but should provisionally be viewed as equivalent to--those produced by DON (Cooney et al, 1974b).…”