Abstract

1. The cardiovascular effects of PPT are as follows: (a) In monkeys, it produces no changes in cardiac rate, rhythm or conduction in subcutaneous doses of 4 mgm./kgm. (b) In dogs, it effectively abolishes the depressor effect of acetylcholine, but in doses as high as 10 mgm./kgm., intravenously, it does not alter the cardiovascular response to histamine or pitressin. (c) In the normal human, doses ranging from 2.5 to 35 mgm. orally, did not produce any changes in blood pressure, cardiac rate, rhythm or conduction.

2. The gastro-enteric effects of PPT are: (a) In monkeys, doses varying from 0.4 to 8 mgm./kgm., subcutaneously, induced spasmolysis in the intact colon rendered hyperactive by morphine. (b) In dogs, doses ranging from 1.0 to 2.5 mgm./kgm., intravenously, induced spasmolysis of normally active and hyperactive ileum and jejunum. (c) In the normal human, 5 and 10 mgm. doses, sublingually, depressed normal gastric motility.

3. The uterine effects of PPT are: (a) No changes were observed after intravenous doses ranging from 1 to 10 mgm./kgm. in the intact, non-pregnant, rabbit uterus or in the intact rat uterus with subcutaneous doses of 0.5-8.0 mgm./kgm. (b) Increase in activity was noted when concentrations ranging from 5 x 10^-4 to 5 x 10^-2 mgm./cc. bathed the isolated strip of the non-pregnant guinea pig.

4. Chronic toxicity: Daily administration of PPT to rabbits in doses of 40 mgm./kgm., subcutaneously, until death (46-68 days) slightly diminished renal and hepatic functions and increased red and white cell counts. The latter effect may be correlated with a progressive anorexia, weight loss, and dehydration. No significant histopathologic changes were produced.

5. General effects of PPT in the human: In doses from 2.5 to 30 mgm., there were no measurable changes in a two-hour observation period on central nervous, cardiovascular or respiratory systems. One subject, of four receiving 35 mgm., experienced vertigo, dimming of vision and chills lasting 80 minutes.