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

The prevention of cerebral vasospasm with OKY-046, an imidazole derivative and a thromboxane synthetase inhibitor, was studied co-operatively at ten neurosurgical services. Intravenous administrations of 2, 5 or 10 mu/kg/minute of OKY-046 were given continuously from the earliest possible day to the 14th SAH-day to 82 patients with ruptured cerebral aneurysm. Sixty-eight patients (83%) showed moderate to high high-density (SAH) in their initial CTs. Angiographic vasospasms were seen in 58 patients, representing 71% of all cases or 81% of the 72 cases for which angiograms were available: the vasospasms of 45 patients (55 or 63%) were moderate to severe. Symptomatic vasospasm occurred, however, only in 27 patients (33%): in 18 of those cases, moreover, the symptoms were mild or transient. The conditions of the patients at one month after the SAH were classified into 9 grades from 0 (normal) to 8 (deceased). Fifty-two patients (63%) were classified as 0 or 1, and 64 (78%) as better than 3 (possible daily life unaided). The administration of OKY-046 was proven to decrease TXB2 in the blood. This paper emphasizes the effectiveness of the drug for symptomatic vasospasm, and supports our previous contention that cerebral microthrombosis may play an important role in the pathogenesis of cerebral vasospasm.

Topics: Acrylates; Adult; Aged; Drug Eruptions; Female; Hemorrhage; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Meclofenamic Acid; Methacrylates; Middle Aged; Recurrence; Subarachnoid Hemorrhage; Thromboxane-A Synthase

The authors report the results of inhibition of thromboxane A2 synthetase in 49 consecutive patients with subarachnoid hemorrhage (SAH). These unselected Grade I to IV patients all had a ruptured aneurysm of the anterior circle of Willis, and were operated on within 72 hours after SAH. Twenty-seven patients were treated postoperatively by an intravenous infusion of sodium (E)-3- [4-(3-pyridylmethyl)-phenyl] -2- propenoate (OKY-1581), a selective inhibitor of thromboxane A2 synthetase, at 5 micrograms/kg/min for 10 to 14 days, and the remaining 22 patients did not receive this drug. Both groups of patients had similar age distribution and preoperative neurological conditions. A suggestive but statistically insignificant improvement was found in postoperative angiographic vasospasm, ischemic symptoms, and overall outcome in the group receiving OKY-1581. The incidence of low-density areas on the postoperative computerized tomography scans was significantly decreased in patients treated with OKY-1581 infusion.

Topics: Acrylates; Adult; Aged; Cerebral Angiography; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Methacrylates; Middle Aged; Rupture, Spontaneous; Subarachnoid Hemorrhage; Thromboxane-A Synthase; Tomography, X-Ray Computed