Studies on drug metabolism by use of isotopes. 23. Metabolic study of 1-butyryl-4-cinnamylpiperazine in the rat during development of tolerance by using two kinds of deuterium-labeled forms.
Mass fragmentographic determination of the plasma, brain, and liver levels of 1-butyryl-4-cinnamylpiperazine (I) and its metabolites in tolerant and nontolerant rats was carried out by using two kinds of deuterium-labeled compounds. 1-Butyryl-4-[a-d2]cinnamylpiperazine (I-d2) was used to develop tolerance and 1-butyryl-4-[arom-d5]cinnamylpiperazine (I-d5) to clarify the metabolic fate of I after I-d2 administration. The present method allowed the clarification of the metabolism of I-d2 and I-d5 independently. In tolerant rats, the brain and liver were lower for I-d5 and higher for I-d5 metabolites than in nontolerant rats. There was no significant difference in the plasma levels of I-D5 between tolerant and nontolerant rats. Our data seem to suggest that development of tolerance to I results from a more rapid metabolism of the drug due to hepatic enzyme induction.
D000818:Animals; D001921:Brain / Q000378:metabolism; D003903:Deuterium; D004361:Drug Tolerance; D008401:Gas Chromatography-Mass Spectrometry; D007553:Isotope Labeling; D008099:Liver / Q000378:metabolism; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D051381:Rats
D010879:Piperazines; D003903:Deuterium