title: Anti-inflammatory/anti-pyretic salicylic acid esters with low gastric ulcerogenic activity.
abstract: The methyl and some other esters of acetylsalicylic and salicylic acids and their derivatives were found to have much lower gastric ulcerogenic activity (when assayed in the stress-sensitized rat) compared with their corresponding acids. There was little or no loss in therapeutic potencies of these salicylate esters as determined by assessment of anti-inflammatory activity (against the carrageenan-induced oedema) and antipyretic activity (against yeast-induced fever in rats. The methyl ester of acetylsalicylic acid (=AME) was almost devoid of gastric irritancy/ulcerogenicity (as observed with acetylsalicylic acid) when given orally to pigs for 10 days. AME had appreciable anti-inflammatory activity in the adjuvant-arthritis model and at high doses (200 mg/kg t.i.d.) was without the lethal effects seen with acetylsalicylic acid. Moreover, no toxic effects were seen after long-term administration of 100-1000 mg/kg/day AME for 3-4 months. The results provide further evidence for the hypothesis that the carboxylic acid moiety of salicylates is a major factor in the gastric ulcerogenic activity of these drugs. The methyl esters of these salicylates may be considered as models for the development of pro-drugs and in some cases may be therapeutic alternatives to acetylsalicylic acid or salicylate.
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001241:Aspirin / Q000031:analogs & derivatives* / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D051381:Rats; D012459:Salicylates / Q000633:toxicity*; D013276:Stomach Ulcer / Q000139:chemically induced*; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D012459:Salicylates; D001241:Aspirin