Studies on the mechanism of the epileptiform activity induced by U18666A. II. Concentration, half-life and distribution of radiolabeled U18666A in the brain.

The concentration, half-life, and distribution in brain of U18666A, a drug that can drastically alter cerebral lipids and induce a chronic epileptiform state, was determined following both acute and chronic drug administration. U18666A specifically labeled with tritium was prepared by custom synthesis. Brain levels of 1 x 10(-6)M and higher were reached soon after giving an acute 10-mg/kg dose (i.

Studies on the mechanisms of the epileptiform activity induced by U186661. I Gross alteration of the lipids of synaptosomes and myelin.

U18666A, an inhibitor of desmosterol reductase (a terminal enzyme in cholesterol synthesis), has been found to produce chronic epileptiform activity in laboratory animals. Since desmosterol might substitute for cholesterol in neuronal membranes without detriment, the present study was undertaken to examine the possibility that this drug-induced epilepsy was related to changes in other brain lipids. Chronic treatment of rat with U18666A, beginning at one day of age, resulted in pronounced decreases in the concentration of phospholipids and increases in gangliosides of brain microsomal, synaptosomal, and crude myelin fractions.

Reactivity of key metabolic sterols in standard colorimetric assays for cholesterol.

The reaction of lanosterol, desmosterol and 7-dehydrocholesterol, key intermediates in cholesterol biosynthesis, were-compared with cholesterol in 3 standard colorimetric assays for cholesterol based on formation of chomogens with acetic anhydride, ferric chloride and ferrous sulfate. Marked differences in the reaction of the sterols in the different assays were due both to formation of chomogens with qualitatively similar spectral patterns but with greatly different extinctions and to formation of chromogens with clearly different absorption maxima. For example, in all assays, cholesterol and desmosterol formed chromogens with very similar absorption spectra but with varying extinctions, whereas the lanosterol chromogen in all assays was different from cholesterol's in both absorption maxima and in extinctions.