Activity of dipyrone on intraplatelet arachidonic acid metabolism: an in vitro study.
The effects of dipyrone on platelet cyclooxygenase and lipoxygenase were investigated in vitro by the study of 1-14C arachidonic acid (AA) conversion by high performance liquid chromatography (HPLC) on washed platelets at seven different drug concentrations (from 5 to 300 micrograms/ml). The effects of dipyrone on thromboxane (TX) B2 generation from endogenous AA were also studied in platelet-rich plasma and in washed platelets by radioimmunoassay. In the study of 1-14C AA metabolism the inhibitory concentration (IC) 50 for TXB2 was 40 micrograms/ml. However, at the lowest drug concentration (5 micrograms/ml) a slight but significant inhibition was found (25.3%, P less than 0.001) and a complete one at 300 micrograms/ml. A relationship between TXB2 inhibition and log drug concentration was found (r = 0.97, P less than 0.001). Lipoxygenase (LO) activity showed an increase of 45.9% at 20 micrograms/ml and of 251.5% at the highest concentration (r = 0.97, P less than 0.001). The inhibition of TXB2 generation from endogenous AA by washed platelets was of the same order of magnitude of the inhibition of TXB2 production from exogenous 1-14C AA. Our results indicate that dipyrone affects intraplatelet AA metabolism at very low concentrations, however its activity, on a molar ratio basis, appears to be lower than that of other non-steroidal anti-inflammatory drugs.
Abbate
R
R
Clinica Medica I, Universita' di Firenze.
Pinto
S
S
Gori
A M
AM
Paniccia
R
R
Coppo
M
M
Neri Serneri
G G
GG
D000328:Adult; D000632:Aminopyrine / Q000031:analogs & derivatives*; D001095:Arachidonic Acids / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004177:Dipyrone / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D013928:Thromboxane A2 / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D000632:Aminopyrine; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D004177:Dipyrone