[Chemical synthesis of phenylbutazone hydroperoxide and testing of the substance for heart action under in vitro and in vivo conditions].
Phenylbutazone (4-n-butyl-1,2-diphenyl-pyrazolidine-3,5-dione) 1 is an easily autoxidable substance which forms a crystalline and stable hydroperoxide 3. The decomposition of 3 yields products which were investigated as metabolites of the drug. In isolated heart preparations of guinea pigs and rabbit hearts in vivo the hydroperoxide 3 shows a significantly stronger cardiodepressive and coronary constricting effect compared to phenylbutazone 1, 4-hydroxy-phenylbutazone 4 and the open-ring decomposition product of the hydroperoxide 5. The results indicate the significance of the hydroperoxide 3 for the total efficiency of phenylbutazone and explain the side effects of the substance.
Mentz
P
P
Institut für Pharmakologie und Toxikologie, Martin-Luther-Universität Halle, DDR.
Schulz
M
M
Kluge
R
R
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010653:Phenylbutazone / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits
D006861:Hydrogen Peroxide; D010653:Phenylbutazone
Chemische Darstellung von Phenylbutazon-hydroperoxid und Prüfung der Substanz auf Herzwirksamkeit unter In-vitro-und In-vivo-Bedingungen.