Effects of leptophos on rat brain levels and turnover rates of biogenic amines and their metabolites.
Leptophos is a potent acetylcholinesterase inhibitor which causes delayed central-peripheral neuropathy. Rats were administered multiple doses of leptophos until motor deficits were observed in rotorod performance in the highest dosage group. Doses lower than the median effective dose were then administered to other rats and alterations of brain catecholamine and serotonin levels and turnover rates were determined. Turnover rates of brain norepinephrine and dopamine were elevated in rats administered cumulative doses of 75 mg/kg leptophos over a 15-day period. Levels of the major dopamine metabolite, 3,4-dihydroxyphenylacetic acid, appeared to be slightly elevated at this dose level and levels of dopamine were also higher than controls. These observations suggest that leptophos increases brain adrenergic activity. Rats administered the same dose levels had significantly reduced serotonin turnover rates. This observation was possibly artifactual, because rats administered a cumulative dose of 225 mg/kg leptophos showed no difference from controls.
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000032:analysis; D007306:Insecticides / Q000633:toxicity*; D010773:Leptophos / Q000633:toxicity*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism
D001679:Biogenic Amines; D007306:Insecticides; D012701:Serotonin; D010773:Leptophos; D004298:Dopamine