Neurotoxicity of deoxycoformycin: effect of constant infusion on adenosine deaminase, adenosine, 2'-deoxyadenosine and monoamines in the mouse brain.
The tight-binding adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF), was continuously infused into mice by intraperitoneal implantation of microosmotic pumps delivering the compound at a rate of 0.16 mg hr-1 kg-1 for up to 6 days. The activity of cerebral adenosine deaminase was nearly totally inhibited. The amount of adenosine and 2'-deoxyadenosine was determined in the brain frozen in liquid nitrogen through the intact skull bone. The concentration of adenosine was about 1 nmol/g, and was essentially not altered following treatment with deoxycoformycin. Deoxycoformycin induced a progressive increase in cerebral content of 2'-deoxyadenosine, which after 1 day of treatment equalled the amount of adenosine. The concentrations of serotonin, dopamine and noradrenaline in the brain were not altered.
D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D003070:Coformycin / Q000031:analogs & derivatives / Q000633:toxicity*; D003839:Deoxyadenosines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D009700:Nucleoside Deaminases / Q000378:metabolism*; D015649:Pentostatin; D012263:Ribonucleosides / Q000633:toxicity*; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
D001679:Biogenic Amines; D003839:Deoxyadenosines; D012263:Ribonucleosides; D003070:Coformycin; D012701:Serotonin; D015649:Pentostatin; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D000241:Adenosine; D004298:Dopamine; D009638:Norepinephrine