1. The influence of the antifilarial
drug diethylcarbamazine citrate (D) and DL-erythro
mefloquine hydrochloride (Mf) on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium was investigated in vitro using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with D (25.5-204 microM) or Mf (24-192 microM) for 30 min at 37 degrees C significantly inhibited PGI2 synthesis in a concentration-dependent manner. 3. D exhibited its inhibitory effect even in presence of exogenous
arachidonic acid (AA) (16.6 microM) whereas Mf lost its inhibitory effect in presence of AA. 4. Pretreatment of
urethane-anaesthetized rats with D (32 mumol kg-1) but not Mf (7.5 mumol kg-1) for 30 min significantly antagonized AA (4 nmol kg-1)-induced
hypotension. 5. Furthermore, D (0.25-0.5 microM) antagonized AA-induced aggregation in rabbit platelet-rich plasma without affecting that of
ADP. 6. D seemed to interfere with the action of the PG endoperoxide synthase (PG
cyclooxygenase) whereas Mf seemed to interfere with the action of
phospholipase A2 (PLA2)
enzyme. 7. D may have exerted its effect via release of toxic O2 radicals whereas Mf effect may have been due to an interaction with PLA2 substrate
phospholipids. 8. The demonstrated inherent property of these two drugs to inhibit the synthesis of the potent
vasodilator, platelet antiaggregatory,
anticonvulsant and antiinflammatory mediator PGI2 may partly contribute towards better understanding of the biochemical mechanisms that underly some of the previously known but poorly understood actions of these drugs.