Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition.
Using flurbiprofen, a chiral anti-inflammatory and analgesic 2-arylpropionic acid derivative, the enantiomers of which are not converted to each other (less than 5%) in rats or man, we obtained evidence that prostaglandin synthesis inhibition is primarily mediating the anti-inflammatory activity but prostaglandin synthesis independent mechanisms contribute to the analgesic effects. Thus, the S-form inhibited prostaglandin synthesis, inflammation and nociception in rats. The R-form had much less effect on prostaglandin synthesis and did not affect inflammation. It did, however, block nociception in rats almost as potently as the S-form. S-flurbiprofen, in contrast to the R-form, was clearly ulcerogenic in the gastrointestinal mucosa. These results indicate additional molecular mechanisms of analgesia and suggest the use of R-arylpropionic acids as analgesics.
Brune
K
K
Department of Pharmacology and Toxicology, University of Erlangen-Nürnberg, Federal Republic of Germany.
Beck
W S
WS
Geisslinger
G
G
Menzel-Soglowek
S
S
Peskar
B M
BM
Peskar
B A
BA
D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004064:Digestive System / Q000187:drug effects; D005480:Flurbiprofen / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D010146:Pain / Q000188:drug therapy*; D011448:Prostaglandin Antagonists / Q000627:therapeutic use*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D005480:Flurbiprofen; D001241:Aspirin