The effect of inhibiting brain thromboxane biosynthesis on pentylenetetrazole-induced seizure threshold.
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.
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D001923:Brain Chemistry; D005260:Female; D007093:Imidazoles; D007213:Indomethacin; D008689:Methacrylates; D051379:Mice; D010433:Pentylenetetrazole; D011453:Prostaglandins / Q000032:analysis; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D013929:Thromboxane B2 / Q000502:physiology*; D013931:Thromboxanes / Q000502:physiology*
D007093:Imidazoles; D008689:Methacrylates; D011453:Prostaglandins; D013931:Thromboxanes; C039242:dazmegrel; D013929:Thromboxane B2; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D010433:Pentylenetetrazole; D007213:Indomethacin