Abstract
The metabolic fate of a new analgesic agent, 1-n-butyryl-4-cinnamylpiperazine hydrochloride (BCP-HCl) in the rat was investigated in vivo and in vitro.
The following four urinary metabolites were detected in addition to the unchanged drug by both the thin-layer (TLC) and gas-liquid chromatography (GLC); 1-n-butyrylpiperazine (I), 1-n-butyry1-4-(4'-hydroxycinnamyl) piperazine (III), 1-(4'-hydroxycinnamyl)-piperazine (IV) and 1-cinnamylpiperazine (V). These were isolated and identified physicochemically (ultraviolet, infrared and mass spectrometry and mixed melting point test). In addition to the above metabolites, piperazine hexahydrate (II) and two unidentified products, UK-1 and UK-2 were detected in the urine by the TLC but not by the GLC.
In the bile BCP, I, III, and IV were detected in addition to the glucuronide and sulfate conjugates of III and IV. One unknown metabolite corresponding to the urinary UK-1 was also detected by the TLC of the biliary metabolites hydrolyzed with β-glucuronidase or arylsulfatase.
In vitro incubation of BCP-HCl with the post-mitochondrial fraction of the rat liver resulted in the formation of the four metabolites, I, III, IV and V.
