Abstract
N-Cyanomethylmethamphetamine (CMMA), N-formylmethamphetamine (FMA) and methamphetamine (MA)were given intraperitoneally to mouse and rat in doses of 3 mg/kg. The major matabolites of CMMA, FMA and MA in plasma were determined at short intervals after administration by GC-MS to obtain the area under the concentration-time curve (AUC).Regarding the plasma concentration of FMA after CMMA administration, a definite species difference was observed between mouse and rat. In rats given CMMA, FMA was the major component, followed by MA, amphetamine(AP), CMMA and N-formylamphetamine (FAP). In mice given CMMA, MA was major component, followed by AP, FMA, CMMA and FAP. However, it was demonstrated that MA is also non-enzymatically produced from CMMA in plasma. Following FMA administration to rats, FMA was the major component in the plasma, showing the largest AUC value of the four metabolites, FMA, FAP, MA and AP. Following FMA administration to mice, MA showed the largest AUC value, followed by FMA, FAP and AP which were present at low levels even 5 min after injection and were scarcely detectable at 60 min. These results suggest two main mechanisms involved in the metabolism of the N-cyanomethyl group, one of which is the formation of MA by elimination of cyanoformaldehyde from N-α-hydroxylated CMMA and the other which is the formation of FMA by elimination of hydrogen cyanide from N-α-hydroxylated CMMA. The formation of FMA from CMMA was the predominant pathway in rats but not in mice.
