Imidazolines metabolism

Tetrahydroquinoxalines such as the ester (20, R = H) have been studied as model compounds for tetrahydrofolic acid. The latter has a vital role in one-carbon metabolism. On treating the ester with formaldehyde, in aqueous dioxan, the fused imidazoline 40 is isolated. Compound 40 undergoes acid-catalyzed rearrangement to the diazepine 42. Using a suitably blocked ester (20, R = Me), it has been possible to isolate the formaldehyde condensation product 41, formed by interaction with nitrogens 4 and 10. It is suggested that a compound of this type is formed prior to the imidazoline 40. ... 

Veiiiquette R-A, Kossover R, Previs S-F, et al. Lipid-lowering actions of imidazoline antihypertensive agents in metabolic syndrome X. Naunyn Schmiedebergs Arch Pharmacol 2006 372 300-312. 

Doss GA, Miller RR, Zhang Z, Teffera Y, Nargund RP, Palucki B, Park MK, Tang YS, Evans DC, Baillie TA, Steams RA (2005) Metabolic activation of a 1, 3-disubstituted piperazine derivative evidence for a novel ring contraction to an imidazoline. Chem Res Toxicol 18 271-276... 

Metabolism 95% of tiie drug is metabolized by the cytochrome P450 system, primarily by the CYP1A2 isoenzyme. Metabolism is via oxidation of the imidazoline part of the molecule. There are three main metabolites and fom minor identified in humans, all of which are pharmacologically inactive. Tizanidine is extensively metabolized by the liver with only 3% excreted imchanged in the m-ine. The drug is eliminated from the body mostly in the mine (66%) and the rest (23%) in the feces. Elimination half-life is 2-4 hours [1-3]. 

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