title: Pure enantiomers of 2-arylpropionic acids: tools in pain research and improved drugs in rheumatology.
abstract: The mode of action of aspirinlike drugs in pain is widely referred to as inhibition of prostaglandin synthesis. Salicylic acid, however, at low doses, is an analgesic but not a potent anti-inflammatory agent. This "enigma" may be resolved by recent findings employing 2-arylpropionic acids. Pure enantiomers of these chiral drugs show a different pharmacodynamic and pharmacokinetic profile. Using pure enantiomers of flurbiprofen, ibuprofen, and ketoprofen, we could show that (1) R-enantiomers of these drugs are inverted to S-enantiomers to a different degree in different species, including humans, (2) the pharmacokinetic parameters of both pure enantiomers differ in a drug- and a species-specific manner, and (3) both enantiomers exert differential analgesic effects. It appears particularly interesting that R-flurbiprofen, for instance, which is not or only to a small extent inverted in humans and rats, is practically devoid of prostaglandin synthesis inhibition in vitro. Consequently, in line with current thinking, R-flurbiprofen is not toxic to the gastrointestinal tract and shows no anti-inflammatory effects. In contrast to current concepts, however, this enantiomer does exert analgesic activity in different models of pain and nociception. It is concluded that R-flurbiprofen and, possibly, other R-enantiomers of 2-arylpropionic acids may exert novel analgesic effects independently of peripheral prostaglandin synthesis inhibition in inflamed tissue.
authors.affiliation: Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuernberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Brune
authors.forename: G
authors.initials: G
authors.lastname: Geisslinger
authors.forename: S
authors.initials: S
authors.lastname: Menzel-Soglowek
mesh_terms: D000818:Animals; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use; D007660:Ketoprofen / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy*; D011422:Propionates / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D012106:Research; D012216:Rheumatic Diseases / Q000188:drug therapy*; D013237:Stereoisomerism
chemical_list: D011422:Propionates; D007660:Ketoprofen; D007052:Ibuprofen