Piperazine nitrosation

Piperazine and its salts are readily absorbed from the gastrointestinal tract, but nitrosation may occur in the stomach (32). The major portion of the absorbed drug is metabolized in tissues and the remainder, which is about 30-40%, is excreted in the urine. Piperazine is detectable in the urine as early as 0.5 h after drug administration. Although there is a wide variation in the rates at which piperazine is excreted by different animal species, urinary excretion is practically complete within 24 h. 

Although nuclear C-nitrosopyrazines can be made, they appear to be too unstable for isolation and characterization as such in contrast, many N-nitrosated derivatives of piperazine or other partially reduced pyrazines are quite stable. 

A few reactions of A-nitrosopiperazines have been reported recently. At least some such piperazines undergo facile transnitrosation and may be used to nitrosate other secondary bases or the like. For example, 2,6-dimethyl-1,4-dinitrosopiperazine (31) with piperidine (32), at pH 1.7 in the presence of sodium thiocyanate as catalyst, gave 2,6-dimethyl-4-nitrosopiperazine (33) and 1-nitrosopiperidine (34).763,cf-954... 

Many other secondary amines have been identified in tobacco smoke but for most of them no corresponding NNA has been identified in smoke. These include a series of (V-substituted anilines, all amenable to A-nitrosation XXXV. Others include the alkyl derivatives of pyrrolidine XXXVI, piperazine XXXVII, andpiperidine XXXVIII. The amines pyrrolidine (XXXVI), piperazine (XXXVII, and 1,2,3,6-tetrahydropyridine (XXXIX) have been identified in cigarette MSS but not piperazine (XXXVII) (see structures in Table XV-7). For each piperazine, mono- and... 

Key words Nitrosation reactions 0(-, B-, Y-cyclodextrin, dimethyl-6-cyclodextrin piperazine ethaiributol cim idine 1-etdiedrine fencamfamine. 

The nitrosation bdiaviours of piperazine, ethairtoutol, cimetidine, 1-ephedrine and fencamfamine without CDs and in presence of CDs were determined. 

Addition of CDs cannot generally avoid or inhibit the in vitro nitro-sation of the five drugs. The reaction rates of the fast nitrosatable drugs piperazine, ethambutol and cimetidine are not influenced by the three CDs. But, B-, /-CD and 2,6-DIMEB catalyze significantly the nitrosation of the slow er nitrosatable efbedrine and fencamfamine. 

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