N,N-dimethylamphetamine (DMA) is a methamphetamine analogue known to be a weaker central nervous system stimulant than methamphetamine. Although a major metabolite of DMA is known to be DMA N-oxide (DMANO), which may be catalysed by flavin-containing monooxygenase (FMO), the specific enzyme(s) involved in this biotransformation has not been identified. In this study, the specific enzyme(s) involved with DMA N-oxidation was characterized by several assays. When DMA was incubated with different human recombinant drug-metabolizing enzymes, including FMOs and cytochrome P450s (CYPs), the formation of DMANO by FMO1 was the most predominant. The Michaelis-Menten kinetic constants for DMA N-oxidation by FMO1 were: K(m) of 44.5 microM, V(max) of 7.59 nmol min(-1) mg(-1) protein, and intrinsic clearance of 171 microl min(-1) mg(-1) protein, which was about twelve-fold higher than that by FMO3. Imipramine, an FMO1-specific inhibitor, selectively inhibited DMA N-oxidation. The resulting data showed that DMA N-oxidation is mainly mediated by FMO1.
This paper describes a simple and convenient simulation method, which uses analytical models for mark and beam patterns. The readout signal of optical disk system is obtained by two-dimensional convolution of Gaussian intensity beam pattern and elliptical mark pattern. Then, signal spectrum is obtained by executing a fast Fourier transform algorithm after adding quantitative MO noise sources within bandwidth. For simulation, the two-dimensional distributions of mark reflectivity and beam intensity were digitized, which enabled us to use easily available algorithm routines in digital signal processing. The resolution of the beam and mark patterns can easily be adjusted by changing the number of bits representing the patterns. Also, various noise sources in the MO disk system can be selectively added using random function generator. Simulated signal spectra were compared with experimental results. The parameters used were as follows: laser beam width was 780 nm, NA was 0.55, signal frequency was 9.4 MHz, duty ratio was 38%, and minimum mark dimension was 0.6 μm by 0.75 μm. Simulated C/N ratio was 50 dB, which was very close to the experimental value of 52 dB.
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