Date of Award


Degree Type


Degree Name

Master of Science in Pharmacology



First Advisor

John J. DeFeo


Several 1-alkylbenzoylpyridinium halides containing alkyl side chains of one to fifteen carbons were screened for pharmacological activity. A comparison of potency was based on the ability to produce mortality in 50 percent of mice (LD 5D). The following parameters were investigated in a select number of compounds representative of the series: acute intraperitoneal LD50 in rats; EDSO (hypotensive) in rats; effects on the autonomic nervous system of anesthetized cats and dogs as indicated by alteratio11s in blood pressure; effects en the nictitating membrane in anesthetized cats; direct effects upon blood vessels employing hind quarter perfusion in intact rats; effects on the isolated perfused guinea pig heart. In mice the trend of acute intraperitonsal toxicity was biphasic. ~he methyl salts were the least toxic , while toxicity sharply increased with the ethyl salts. As the carbon substitution increased to seven, toxicity decreased. Further carbon substitution led to a progressive increase in toxicity. Although fewer compounds were tested in rats, the LD50’s approximately paralleled those of the mice. 3-Benzoyl-1-ethylpyridinium iodide (3-C2-I), 3-benzoyl-1-octylpyridinium bromide (3-CB-Br), and 3-benzoyl-1-pentadecylpyridinium bromide ( 3-C15-Br) produced hypotensive effects in anesthetized rats. The ED50 (hypotensive) increased in that order. Demonstration of hypotensive responses in anesthetized rats led to an investigation of the mechanism of this action& Decreased responses to carotid occlusion and vaga l stimulation 2nd increased responses to injected epinephrine in anesthetized cats and dogs suggested th a t the 3-C2-I and 3-CB-Br exerted a hypotensive response through ganglioplegia. 3-CB-Br was more potent than 3-C2-I. Further testing of 3-C15-~ was discontinued at this time as respiratory failure followed by cardiac arrest occurred, apparently due to excessive quantities of fluid in the respiratory passages. 3-Benzoyl-1-dodecylpyridinium bromide also elicited this response. The ability of 3-C2-I and 3-CB-Br to block the normal response of the nictitating membrane in cats by electrical stimulation of the pre~ ganglionic cervical sympathetic nerve was tested 3-CB-Br was more potent than 3-C2-I in this test. The flow rates of perfusions of the hind quarter vasculature of the intact rats were unaffected by doses up to the equivalent ED 50 (hypotensive) 3-C2-I and 3-CB-Br showed cardiodepressant and cardiotoxic effects on the isolated guinea pig heart, although a direct dose effect relationship could not be shown. 3-CB-Br was more potent than 3-C2-I in producing cardiac arrest. The results of these experiments support the hypothesis that 3-C2-I and 3-CS-Br exert a hypotensive effect through ganglioplegia, unabetted by direct vasodilation. A depressant action on the heart may contribute to the hypotension induced by ganglioplegia.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.