Towards the Bioassay of a Novel Series of Synthetic - Putative Fk Anti-inflammatory Agents
The drugs used conventionally in the treatment of inf 1 amatory states are either steroidal or non-steroidal. The emergence of FK compounds - a series which comprises several novel compounds unique in having bridged the time - honoured gap between steroidal3 or non-steroiduls represents a synthetic feat which conraands admiration. Previous few workers have screened activity of thesa compounds and the already accrued data suggest that these compounds display potent anti-inflatanatory action in the rat and results from castor oil test and Carageenan rat paw oedema testify to tliesu effects. In pursuit of the mechanism of action of the FKs using "The Delay in Castor oil-induced diarrhoea" (an acutenon-invasive model) und confirmed by the castor oil-induced colonic water flux (an acute invasive model), the results obtained in this present work are suggestive of PG-synthetase inhibition. Qualitative assessment of the rasults indicate that some of the compounds are more potent than Indometliacln - an established PC synthetase inhibitor. - Consistent with the now widely hold and established view that PC synthetase inhibitors show shared, side effects namely: gastrointestinal toxicity, nephrotoxicity, inhibition of platelet aggregation and delay in pregnancy and parturition, I embarked on the investigation of the renal side effects of these FK compounds and results obtained displayed varying extents of side effects on water and mineral activity in the kidney, with some causing extreme loss of sodium and potassium while others with potential diuretic side effects. Further, this work indicates the acute need for more sensitive and direct models to really establish the mechanism of action and the potency of these novel compounds. Undoubtedly, the extent of their side effects needs to be urgently established and the renal data I have presented be confirmed by further experimentation, if they have to achieve any future place in therapy of iu£luuonutary status.
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