Effects of thromboxane synthetase inhibitor (RS-5186) on experimentally-induced cerebral vasospasm.

Abstract

RS-5186, which inhibits thromboxane A2 (TXA2) synthetase activity, ameliorated delayed cerebral vasospasm in a canine two-hemorrhage model. Subarachnoid hemorrhage was induced in 15 dogs, which were divided into two groups. In the RS-5186-treated group (9 dogs), 50 mg kg-1 of RS-5186 was administered twice a day for seven days. The remaining six dogs without administration of RS-5186 were used as a control group. In the RS-5186-treated group, the angiographic diameter of the basilar artery on Day 7 after subarachnoid hemorrhage was constricted to 60.9% +/- 11.6% (n = 9, mean +/- SD) of that on Day 0, before subarachnoid hemorrhage. The corresponding value was 42.8% +/- 6.1% (n = 6) in the control group. There was a statistically significant difference between these percentages. In the RS-5186-treated group, plasma thromboxane B2 level on Day 7 was 144.3 +/- 28.1 pg ml-1 (n = 4), which was lower than the 815.5 +/- 162.0 pg ml-1 (n = 4) in the control group (p < 0.0005). The plasma 6-keto-prostaglandin F1 alpha level on Day 7 was 180.5 +/- 66.5 pg ml-1 (n = 4) in the RS-5186-treated group, and higher than 107.3 +/- 12.4 pg ml-1 (n = 4) in the control group (p = 0.0734). Thus, administration of RS-5186 reduced TXA2 plasma level and had a beneficial effect on angiographically-detected delayed vasospasm.

• Authors: H Takeuchi, M Tanabe, H Okamoto, M Yamazaki
• Journal: Neurological research (Neurol Res) Vol. 21 Issue 5 Pg. 513-6 (Jul 1999) ISSN: 0161-6412 [Print] England
• PMID: 10439434 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Neuroprotective Agents
• Thiophenes
• RS 5186
• Thromboxane A2
• Epoprostenol
• Thromboxane-A Synthase

Topics

• Animals
• Basilar Artery (drug effects, pathology)
• Dogs
• Drug Evaluation, Preclinical
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Epoprostenol (biosynthesis)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Subarachnoid Hemorrhage (complications)
• Thiophenes (pharmacology, therapeutic use)
• Thromboxane A2 (biosynthesis)
• Thromboxane-A Synthase (antagonists & inhibitors, physiology)
• Vasospasm, Intracranial (drug therapy, enzymology)