Subject(s)
Horses/metabolism , Methocarbamol/pharmacokinetics , Administration, Oral , Age Factors , Animals , Biological Availability , Breeding , Female , Half-Life , Injections, Intravenous/veterinary , Intestinal Absorption , Male , Methocarbamol/administration & dosage , Physical Conditioning, Animal , Regression Analysis , Software , Tissue DistributionABSTRACT
Fusion of fagaronine (1) afforded N-demethyl fagaronine (2) and two minor desmethyl products. Through examination of spectral properties and derivatization, the structures were deduced to be 3, a tetramethoxy derivative, and 5, a derivative bearing a hydroxy (rather than a methoxy) group at position-8. Acetylation of 2 afforded a monoacetate derivative (4), and similarly, a diacetate (6) was produced from 5. Compounds 2-6 were substantially less cytotoxic than 1, as judged by KB or P-388 cell culture assays, supporting the functional importance of the quaternary nitrogen atom. The results obtained to date for fagaronine in tumor panel-testing are also presented, and the marginal cytotoxic activity demonstrated by compounds 5 and 6 against cultured P-388 cells is discussed in terms of mechanisms of action of the parent compound.
