ABSTRACT
Velnacrine is a centrally acting anticholinesterase which has been considered for use in the treatment of Alzheimer's disease. If proven to be of value, it will be used concurrently with other medications. Its potential to cause interaction is, therefore, important to study. The aim of this work was to investigate velnacrine as an inhibitor of hepatic oxidative enzymes. The effects of velnacrine on antipyrine metabolism in isolated rat hepatic microsomes were compared to those of cimetidine. Aliquots of 200, 250 and 300 micrograms/ml antipyrine were incubated alone, with 20 micrograms/ml cimetidine and with each of 20, 50 and 100 micrograms/ml velnacrine. The concentrations of antipyrine and of its metabolites, 3-hydroxymethylantipyrine, 4-hydroxyantipyrine and norantipyrine were assayed by reverse phase high performance liquid chromatography. Cimetidine inhibited production of all three metabolites. Velnacrine did not affect 3-hydroxymethylantipyrine production. Mean inhibition of 4-hydroxyantipyrine production of 15%, 30% and 25% (P < 0.01), and of 14%, 25% and 12% of norantipyrine production (P < 0.01) occurred. These results indicate that velnacrine may inhibit the enzymes responsible for the metabolism of antipyrine to norantipyrine and 4-hydroxyantipyrine. The clearance rate of drugs that are metabolised through the hepatic oxidase system may, therefore, be reduced in the presence of concurrent treatment with velnacrine.
Subject(s)
Cholinesterase Inhibitors/pharmacology , Enzyme Inhibitors/pharmacology , Mixed Function Oxygenases/antagonists & inhibitors , Tacrine/analogs & derivatives , Animals , Antipyrine/metabolism , Cimetidine/pharmacology , Cytochrome P-450 Enzyme Inhibitors , Cytochrome P-450 Enzyme System/metabolism , Isoenzymes/antagonists & inhibitors , Isoenzymes/metabolism , Liver/drug effects , Liver/enzymology , Male , Rats , Rats, Wistar , Tacrine/pharmacologyABSTRACT
The development of the computer-controlled microscope system described has made it possible to estimate accurately the contribution made to the muscle fibre population by both Type 1 and Type 2 fibres. This method is more convenient, and at least as accurate as manual methods. It is also possible to measure the size of the individual fibres using this system. The system has been applied to this study of the spinal muscles in scoliosis. The results show that there is a difference in the ratio of Type 1 to Type 2 fibres in the spinal muscles on the 2 sides of the curve. The difference is found only at the apex of the curve. The results demonstrate that there are more Type 2 fibres on the concavity of the curve at the level of the apex. This difference is due to a disparity in the number of each fibre type rather than a difference in their relative sizes. The imbalance of Type 1 fibres at the apex of the curve may provide a sustained muscle pull on the spine so causing a curve convex to that side.
