Effects of single oral doses of lysine clonixinate and acetylsalicylic acid on platelet functions in man.
Lysine clonixinate is an analgesic drug with a so far unknown mechanism of action. We have determined its effect on platelet cyclooxygenase in man. Biosynthesis of thromboxane (TX)B2 and prostaglandin (PG)F2 alpha in clotting whole blood ex vivo as well as collagen-induced platelet aggregation measured before and at various time points after oral administration of 125 mg lysine clonixinate were compared to results obtained with 500 mg acetylsalicylic acid (ASA). While biosynthesis of both TXB2 and PGF2 alpha measured radioimmunologically was inhibited significantly 2.5 h, but not 6 h, after administration of lysine clonixinate, inhibition by ASA was much greater and still highly significant after 48 h. Similarly, collagen-induced aggregation of platelet-rich plasma was inhibited for a longer period and to a greater extent after administration of ASA than after lysine clonixinate. Our results indicate that lysine clonixinate is a cyclooxygenase inhibitor of moderate potency. It remains to be investigated whether mechanisms other than inhibition of cyclooxygenase contribute to the analgesic activity of lysine clonixinate.
Pallapies
D
D
Department of Pharmacology and Toxicology, Ruhr University, Bochum, Germany.
Muhs
A
A
Bertram
L
L
Rohleder
G
G
Nagyiványi
P
P
Peskar
B A
BA
D000284:Administration, Oral; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D003002:Clonixin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003094:Collagen / Q000008:administration & dosage / Q000009:adverse effects; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D015237:Dinoprost / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D013929:Thromboxane B2 / Q000097:blood
D016861:Cyclooxygenase Inhibitors; C089163:lysine clonixinate; D013929:Thromboxane B2; D003094:Collagen; D015237:Dinoprost; D008239:Lysine; D001241:Aspirin; D003002:Clonixin