THE PHARMACOLOGICAL PROPERTIES OF NORBORMIDE, A SELECTIVE RAT TOXICANT

¹ Department of Pharmacology, Research Division, McNeil Laboratories, Incorporated, Fort Washington, Pennsylvania

The pharmacological properties of 5-( hydroxy--2-pyridylbenzyl)-7-(-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide, initially designated as McN-1025 and subsequently as norbormide, are described.

This substance was shown to be a selective rat toxicant. The oral LD50 for the Norawy rat was approximately 10 mg/kg while mammals other than those in genus Rattus, as well as birds, were resistant to this material. For example, in the hamster, the most susceptible of nonrat species, the LD50 was 140 mg/kg, while in cats, dogs, pigs, monkeys, mice, birds and other, 1000 mg/kg orally produced neither death nor abnormalities. Indirect dermal studies indicate that man is probably not susceptible to the toxic action of this substance.

Norbormide produces an extreme irreversible peripheral vasoconstriction in rats. It is probable that this vasoconstriction induces local ischemic changes which lead to death of a number of organs and systems and to the death of the animals.

Vasoconstriction and circulatory changes do not occur in other species, and no insight into the mechanism of selective toxicant properties of this substance is available.

Norbormide seems to be ideally suited for rodenticidal use in being highly toxic and yet well accepted by rats. It is very safe for other species.

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