The monamine oxidase (MAO) inhibitors harmaline, tranylcypromine, deprenyl, clorgyline and iproniazid were injected intraperitoneally for five days to rabbits at doses that produced significant MAO inhibition. The first three inhibitors raised the concentrations of pyruvate and lactate in blood, decreased the activity of erythrocyte transketolase (TK) and increased the thiamin pyrophosphate (TPP) effect. The drugs also produced anorexia and loss of body weight. The changes were suggestive of an adverse effect on the thiamin status. Clorgyline and iproniazid, however, raised the blood concentrations of pyruvate and lactate but did not affect significantly erythrocyte TK activity or TPP effect. Treatment of rabbits for 14 days with the thiamin antagonists pyrithiamin (20 μg kg-1) or oxythiamin (0.8 mg kg-1) produced a significant drop in TK activity and increase in the lactate and pyruvate concentrations as well as an increase in TPP effect. Pyrithiamin (5, 10 or 20 μg kg-1, 14 days) lowered siginficantly the activity of MAO in the liver and brain of rabbits. Treatment with the other antagonist, oxythiamin, at doses of 0.2 or 0.4 mg kg-1 for 14 days had no significant effect on MAO activity. At a dose of 0.8 mg kg-1 a significant drop in MAO activity occurred. A pair-feeding trial indicated that the biochemical changes produced in animals treated with MAO inhibitors were attributable to the drugs per se, and not to the ensuing anorexia. Thiamin (100 μg kg-1, subcutaneously) when given concomitantly with pyrithiamin, oxythiamin, harmaline, deprenyl and tranylcypromine was effective in preventing the development of thiamin deficiency.
|Number of pages||7|
|Journal||British Journal of Pharmacology|
|Publication status||Published - 1985|
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