3-methyl salicylic acid: A long acting salicylate which decreases free fatty acid mobilisation and plasma cholesterol

A. N. Howard, D. E. Hyams, W. Everett, I. W. Jennings, G. A. Gresham, A. Bizzi, S. Garattini, E. Veneroni, T. A. Miettinen

Research output: Contribution to journalArticlepeer-review


A comparative study has been made of the action of 3-methyl salicylic acid, a derivative which has a much longer half-life than salicylic acid in man, on free fatty acid mobilisation and plasma cholesterol in the rat, rabbit, baboon and man. 3-Methyl salicylic acid decreased plasma free fatty acids in rats exposed to conditions of increased mobilisation, such as fasting, cold, and treatment with noradrenaline and ACTH. Evidence was obtained that a dose equivalent to salicylic acid given shortly before test was more effective. As for salicylate, 3-methyl salicylate decreased the in vitro production of FFA and glycerol liberated in vitro by the incubated rat epididymal fat pad. Administration of 3-methyl salicylic acid (100 mg/kg, body weight) reduced plasma cholesterol from 7 to 45% in baboons given an atherogenic, cholesterol-containing diet for one month. In acute experiments, the drug caused a marked choleresis in which the volume and excretion of bile acids but not cholesterol was increased. In the rabbit, the drug (100 mg/kg) caused a decrease in fasting FFA for up to four hours, followed by a large elevation. Inclusion of the drug in the diet of animals given a semi-synthetic diet of low cholesterol content did not reduce hypercholesterolaemia or the extent and severity of atherosclerotic lesions in the aorta. Administration of 0.9 g orally to fasting patients caused a 50% reduction in elevated plasma FFA after four hours and even after twelve hours the values were still subnormal. A double-blind control trial of nine hypercholesterolaemic and eight normal patients was conducted over twelve to eighteen months. Subjects in the hypercholesterolaemic group on chronic dosage (0.9-1.8 g per day) showed a fall of 25% in the mean plasma cholesterol, but there was no change in normal patients. Side effects, the chief of which were drowsiness and vomiting precluded the use of 3-methyl salicylate as a therapeutic agent in man.

Original languageEnglish
Pages (from-to)244-253
Number of pages10
JournalEuropean Journal of Pharmacology
Issue number2
Publication statusPublished - 1971


  • 3-Methyl salicylic acid
  • Atherosclerosis
  • Bile acids
  • Cholesterol
  • Fatty acids, free
  • o-Cresotinic acid
  • Plasma cholesterol

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology


Dive into the research topics of '3-methyl salicylic acid: A long acting salicylate which decreases free fatty acid mobilisation and plasma cholesterol'. Together they form a unique fingerprint.

Cite this