title: Effect of R and S enantiomers of naproxen on aggregation and thromboxane production in human platelets.
abstract: The effects of R and S enantiomers of naproxen [(+)-6-methoxy-alpha-methyl- 2-naphthaleneacetic acid] were studied on platelet aggregation and on the production of thromboxane B2 from collagen-stimulated human platelets in order to determine the effect of each enantiomer in terms of cyclooxygenase inhibition. S-Naproxen caused inhibition of platelet aggregation in platelet-rich plasma and washed human platelets in a concentration-related fashion in the range 1-80 micrograms/L. A similar concentration-related suppression was noted for R-naproxen, but this inhibition was significantly less than that induced by S-naproxen for all concentrations except 1 micrograms/L. Similarly, both R- and S-naproxen (1-80 micrograms/L) caused a concentration-dependent suppression of thromboxane B2 production from platelet-rich plasma. These values were significant at all concentrations of drug (10-80 micrograms/L) except at 1 micrograms/L. Significant differences in thromboxane B2 production from washed human platelets were noted at concentrations of 10 and 25 micrograms/L. The findings support previous studies reported in the literature that S-naproxen is more active than R-naproxen. Our findings that S-naproxen is more active than R-naproxen on collagen-stimulated platelet aggregation and prostaglandin production suggest that the findings of greater activity of S isomer over the R isomer in animal models of inflammation may be a direct expression of the differential action on prostaglandin synthesis.
authors.affiliation: Department of Medicine Laboratory for Inorganic Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: W F
authors.initials: WF
authors.lastname: Kean
authors.forename: C J
authors.initials: CJ
authors.lastname: Lock
authors.forename: J
authors.initials: J
authors.lastname: Rischke
authors.forename: R
authors.initials: R
authors.lastname: Butt
authors.forename: W W
authors.initials: WW
authors.lastname: Buchanan
authors.forename: H
authors.initials: H
authors.lastname: Howard-Lock
mesh_terms: D003094:Collagen / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009288:Naproxen / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013237:Stereoisomerism; D013928:Thromboxane A2 / Q000097:blood; D013931:Thromboxanes / Q000097:blood*
chemical_list: D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D013928:Thromboxane A2; D009288:Naproxen; D003094:Collagen