The distribution of orally administered (-)-deprenyl-propynyl-14C and (-)-deprenyl-phenyl-3H in rat brain.

Using alternatively labelled (-)-deprenyl (3H label in the ring and 14C in the propargyl group) the distribution of the compound was studied in 15 brain regions and the plasma of rats over a period of 96 h, after oral administration of 1.5 mg/kg of (-)-deprenyl. The compound is rapidly absorbed (within 15-30 min) from the gastrointestinal tract, as indicated by its high plasma level. It penetrates to the central nervous system, where it reaches a peak level within 45-60 min. During the first 2 h in the plasma the 14C label, whilst in cerebral tissues during the whole period of the experiment the 3H tracer dominates. The difference in the ratio of 3H to 14C radioactivity (compared to the 0 time relation) develops as early as in the first 15 min, which indicates the operation of a rapid "first pass" biotransformation of the compound. Our data represent the tissue molar concentration -time curves of (-)-deprenyl calculated from both the 3H and 14C radiolabels. A ratio of 1 of the concentrations of the two tracers would indicate that the molecule remained unchanged. The changes in the ratio, therefore, suggest the formation of considerable quantities of metabolites (methylamphetamine and amphetamine) and their presence in the brain. The difference between the area under the curves (AUC0-t for 3H and AUC0-t for 14C) represents the amount of metabolites expected to be formed during the experiment. The concentration of the metabolites should be taken into account while evaluating the pharmacological effect of (-)-deprenyl. We proved earlier that a dose of 1.5 mg/kg of (-)-deprenyl completely blocks MAO-B activity in the central nervous system. The fast metabolism of the inhibitor indicates that a minor part of the orally administered (-)-deprenyl is sufficient to produce a high level of selective MAO-B inhibition in the brain.

Small circular deoxyribonucleic acid of Drosophila melanogaster: homologous transcripts in the nucleus and cytoplasm.

We have recently characterized small circular DNA of Drosophila cultured cells in terms of its average size, sequence complexity, and homology to intermediate repetitive DNA. We show here that transcripts homologous to small circular DNA are present in various RNA fractions. Nuclear poly(A+), nuclear poly(A-), and polysomal poly(A+) RNA drive 10, 7, and 20%, respectively, of in vitro labeled small circular DNA tracer into hybrid. Sequences complementary to small circular DNA are at least 10-fold more concentrated in nuclear poly(A+) RNA than in nuclear poly(A-) or polysomal poly(A+) RNA. We do not detect significant homology between poly(A-) cytoplasmic RNA and small circular DNA. Assuming that only the least complex component of small circular DNA is driven into hybrid and that transcription is asymmetric, we use the results obtained here and previously published data to calculate the sequence complexity and relative concentration of nuclear poly(A+), nuclear poly(A-), and polysomal poly(A+) RNA homologous to small circular DNA.