2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic-acid and Seizures

The effect of inhibiting endogenous brain thromboxane (TXB2) on pentylenetetrazole-induced seizures was studied using the thromboxane synthetase inhibitors OKY-1581 (20 mg/kg) and UK 38,485 (50 mg/kg). Both compounds selectively decreased (greater than 90%) TXB2 production in brain measured after 2 min of convulsive activity but had no effect on brain PGE2, PGF2 alpha, or 6-keto-PGF1 alpha. No effect of these agents on the tonic seizure threshold was observed, whereas 10 mg/kg ip indomethacin, an agent which inhibits both TXB2 and prostaglandin production, reduced the tonic seizure threshold from 78 +/- 2.6 mg/kg in controls to 62 +/- 3.7 mg/kg. Thus, this study concludes that the availability of TXB2 with convulsant activity is unlikely to be a factor in altering tonic seizure activity observed with indomethacin.

Topics: Animals; Brain; Brain Chemistry; Female; Imidazoles; Indomethacin; Methacrylates; Mice; Pentylenetetrazole; Prostaglandins; Seizures; Thromboxane B2; Thromboxanes