THE ACTION AND TOXICITY OF PLATYPHYLLINE AND SENECIPHYLLINE

¹ From the Lilly Research Laboratories, Eli Lilly and Company, Indianapolis

Intravenous injection of lethal or near-lethal doses of seneciphylline in mice, rats, and guinea pigs is followed by tonic convulsions.

Many animals receiving acutely sublethal doses of seneciphylline have a delayed death. Postmortem examination reveals necrosis around the central veins of the liver with infiltration of leucocytes and vacuolation of the cytoplasm of parenchyma cells. This is particularly true with mice and rats. The kidneys are also involved—exhibiting cloudy swelling with venous and glomerular congestion. In a few rats and guinea pigs, a crescent-like structure appears in the glomerular capsule.

Seneciphylline relaxes isolated rabbits' intestines and contracts guinea pigs' or rabbits' isolated uteri. In suitable doses, it occasionally raises arterial blood pressure in anesthetized cats.

Intravenous injection of lethal or near-lethal doses of platyphylline in mice, rats, guinea pigs, and monkeys results in convulsions. The same appear in frogs when the alkaloid is introduced into the lymph sac. The convulsive action is probably exerted upon the medulla, for decerebration has no effect, but destruction of the medulla brings about cessation of convulsions.

No hepatic or renal damages have been observed in mice, rats, or guinea pigs following acutely sublethal doses of platyphylline. In contrast with seneciphylline, there was no delayed death with platyphylline.

Platyphylline appears to have an atropine-like action as evidenced by mydriasis with loss of light reflex, antagonism with acetylcholine, and relaxation of intestinal peristalsis.