Pyrimidinyl nicotinic acid and cerebrocortical necrosis.

Pyrimidinyl nicotinic acid (PNA) exhibits great structural similarities to amprolium, which is a known thiamine antagonist. Experimental cerebrocortical necrosis (CCN) has been induced by oral administration of amprolium. PNA has been demonstrated in ruminai fluid from animals suffering from CCN. The aim of this investigation was to study whether PNA can act as thiamine antagonist and whether it can give rise to CCN. For this purpose PNA was synthesized and was daily given intravenously to a calf. The dose corresponded to roughly 10 times the content of thiamine in the blood. After three weeks the dose was doubled. During the entire experimental period comprising nine weeks no clinical sign of thiamine deficiency or CCN was noticeable. The values for all recorded blood chemical parameters, with the exception of occasional GOT and PK values, were within the normal limits of variation. Rats were used in a similar experiment with the same aim. PNA was homogeneously added to their feed in quantities equivalent to five and 10 times the thiamine content. The rats were clinically healthy throughout the experimental period comprising eight weeks. No significant difference in TK activity and TPP effect was observed between the experimental groups and the control group.