Effect of praziquantel and oxamniquine on prostacyclin synthesis by the rat arterial and myometrial tissues.
1. The influence of the two antischistosomal drugs (+/-) praziquantel and (+/-) oxamniquine on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium in vitro was investigated using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with praziquantel (64-512 microM) or oxamniquine (36-288 microM) for 30 min at 37 degrees C significantly inhibited basal PGI2 synthesis in a concentration-dependent manner (P less than 0.005, n = 5-6). 3. Both drugs failed to inhibit PGI2 synthesis in presence of exogenous arachidonic acid (AA) (16.6 microM). 4. Furthermore, they did not antagonize AA (4 nmol kg-1)-induced hypotension in urethane-anaesthetized rats. Thus, the drugs seemed to act via inhibition of phospholipase A2 enzyme (PLA2). 5. The highly lipophilic drugs may interact with membrane phospholipids resulting in prevention of interaction between the substrates and the enzyme's active site.
el Tahir
K E
KE
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
al-Kharji
A M
AM
Ageel
A M
AM
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D016718:Arachidonic Acid / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D010073:Oxamniquine / Q000008:administration & dosage / Q000494:pharmacology*; D011223:Praziquantel / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D010073:Oxamniquine; D016718:Arachidonic Acid; D011223:Praziquantel; D011464:Epoprostenol