Influence of diethylcarbamazine and mefloquine on PGI 2 synthesis by the rat thoracic aorta and myometrial tissues

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1. 1. The influence of the antifilarial drug diethylcarbamazine citrate (D) and dl-erythro mefloquine hydrochloride (Mf) on PGI 2 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. 2. Pretreatment of the tissues with D (25.5–204 μM) or Mf (24–192 μM) for 30 min at 37°C significantly inhibited PGI 2 synthesis in a concentration-dependent manner. 3. 3. D exhibited its inhibitory effect even in presence of exogenous arachidonic acid (AA) (16.6 μM) whereas Mf lost its inhibitory effect in presence of AA. 4. 4. Pretreatment of urethane-anaesthetized rats with D (32 μmol kg −1) but not Mf (7.5 μmol kg −1) for 30 min significantly antagonized AA (4 nmol kg −1)-induced hypotension 5. 5. Furthermore, D (0.25–0.5 μM) antagonized AA-induced aggregation in rabbit platelet-rich plasma without affecting that of ADP. 6. 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 A 2 (PLA 2) enzyme. 7. 7. D may have exerted its effect via release of toxic O 2 radicals whereas Mf effect may have been due to an interaction with PLA 2 substrate phospholipids. 8. 8. The demonstrated inherent property of these two drugs to inhibit the synthesis of the potent vasodilator, platelet antiaggregatory, anticonvulsant and antiinflammatory mediator PGI 2 may partly contribute towards better understanding of the biochemical mechanisms that underly some of the previously known but poorly understood actions of these drugs.