The biological activity of salicylate and related compounds

Andrews, Muriel Margaret (1959) The biological activity of salicylate and related compounds. PhD thesis, University of Glasgow.

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It is well established that sodium salicylate in moderate dosages increases the metabolic rate of experimental animals and man. The effect on this property of alterations in the chemical structure of salicylate was the subject of the present investigation. The first part of the present work was to determine which compounds within a series of eighteen substituted benzoates were active as metabolic stimulants in the intact rat. These eighteen compounds included the complete series of both the mono and dihydroxybenzoates and the cresotinates. Wistar albino rats were used throughout the investigation and the individual rates of oxygen consumption were measured in a closed circuit manometric apparatus. In these experiments the results were expressed in terms of the difference in rates of oxygen consumption between paired, treated and control rats and the mean difference in rate of oxygen consumption was estimated for each compound. The treated rats were given, by intraperitoneal injection, the sodium salts of the test compounds in the maximum practical doses tolerated. The control animals were given a corresponding volume of normal saline. 2:3-dihydroxybenzoic acid, phthalic acid and 6-methylsalicylic acid were, at the doses used, inactive. Meta- and parahydroxybenzoic acid, 2:4-, 2:5-, 2:6-, 3:4- and 3:5-dihydroxybenzoic acid, o-aminobenzoic acid, salicyluric acid, salicylamide and 5-aminosalicylic acid decreased the metabolic rate. Only the three cresotinic acids, i.e. 3, 4, and 5-methylsalicylio acid possessed the metabolic stimulant property of salicylate. The relative efficacy of the three cresotinates and salicylate as metabolic stimulants was determined by comparison of their respective dose-response curves, and molar potency ratios of the cresotinates relative to salicylate were calculated. Ortho-cresotinate was the most powerful with a ratio of 2.61, meta- and para-cresotinate were of the same order with values of 1.78 and 1.89 respectively. Two possible explanations of the higher potencies of the cresotinates were considered. No difference in the primary action of the drugs was established by determining the effect on rate of oxygen consumption of a mixture of ortho-cresotinate and salicylate. The other possibility considered was that the rates of detoxication and excretion of the cresotinates differed among themselves and from salicylate. No differences in rates of disappearance of the drugs from the blood were found. This finding implies that the relative potencies of the cresotinates and salicylate as metabolic stimulants in the intact rat are a reflection of true potency differences at the tissue level. The reports of previous workers have been presented and the significance of the present results discussed.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: J Reid
Keywords: Pharmacology
Date of Award: 1959
Depositing User: Enlighten Team
Unique ID: glathesis:1959-72589
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06

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