Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review of the clinical studies of thromboxane synthase inhibitors (TXSIs) and thromboxane receptor blocking drugs (TXRBs) covers the years 1981 to the present. Clinical studies on TXSIs include those in normal volunteers as well as those in patients with angina, peripheral vascular disease and Raynaud's syndrome, pulmonary hypertension, cerebral vasospasm, hepatorenal syndrome, adult respiratory distress syndrome, and those on cardiopulmonary bypass and hemodialysis. The compounds studied include dazoxiben, dazmagrel, CGS 13080, CV 4151, OKY 1581, OKY 046, and U 63557A. In volunteers, single-dose studies have demonstrated inhibition of thromboxane A2 (TXA2) formation, with some small increases in bleeding time but no marked effect on platelet aggregation. In general, the compounds tested were ineffective in both chronic stable angina and vasospastic angina but caused symptomatic improvement in patients with unstable angina. The TXSIs studied were found to produce no consistent effects in any of the other clinical conditions. Since none of the compounds tested produced a sustained inhibition of TXA2 synthesis, the disappointing clinical results with this class of drugs may be due to an incomplete blockade of thromboxane synthase with the dosage regimens used. Possible alternative or additional reasons for the general lack of success with TXSIs could be that some of the diseases studied do not involve TXA2 or that accumulating prostaglandin endoperoxides in the presence of thromboxane synthase inhibition substitute for TXA2 in causing platelet aggregation. TXRBs rely for their efficacy only on blockade of the TXA2 receptor and antagonize the deleterious effects of both TXA2 and prostaglandin H2 equally, so they represent a simpler pharmacological approach than TXSIs. Such drugs include AH 23848, GR 32191, BM 13.177, BM 13.505, and SQ 28668. All of these compounds are inhibitors of platelet aggregation induced by TXA2 or by its stable mimetic, U-46619. AH 23848 was ineffective in patients with stable angina but did benefit patients with peripheral vascular disease. BM 13.177 has also proven effective in preventing restenosis after angioplasty, occlusion of coronary artery bypass grafts, and the deleterious effects of TXA2 in renal disease. From these preliminary studies, it would appear that TXRBs may offer greater clinical potential than TXSIs. Further studies currently underway with TXRBs to resolve this question include those in unstable angina, angioplasty, peripheral vascular disease, renovascular hypertension, and cyclosporine nephrotoxicity.
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PMID:Preliminary clinical studies with thromboxane synthase inhibitors and thromboxane receptor blockers. A review. 213 20

24 angina pectoris patients were treated with Codonopsis pilosulae (CP) oral solution 20 ml (containing crude CP 20 g) thrice daily for 7 days, other 10 cases were treated by aspirin 0.5 g per day for a week as the control group. After treatment, in the CP group, the plasma level of TXB2 was obviously reduced from 156.76 +/- 11.87 pg/ml to 125.01 +/- 8.85 pg/ml (means +/- S means), the inhibitory rates was 15. 67% (P less than 0.05), and of 6-keto-PGF1 alpha (6-K) was not markedly changed (P greater than 0.05). In the aspirin group, TXB2 was also reduced significantly (P less than 0.05); 6-K was reduced more than that of CP group, the inhibitory rate was 24.33 +/- 9.40% (P less than 0.05). To reveal the mechanism of CP action on the synthesis of TXA2 and PGI2, the porcine lung microsome was used as the donor of cyclooxygenase, thromboxane synthase and prostacyclin synthase, the effects of CP on the formation of TXB2 and 6-K from arachidonic acid (AA) or endoperoxides were measured by RIA respectively. The results showed that both the levels of the formation of TXB2 from AA or endoperoxides were markedly reduced by CP in a dose-dependent (at doses of 3-300 mg/ml). The synthesis of TXB2 was distinctly inhibited alone with a dose of 100 mg/ml CP, which suggested that CP might be an inhibitor of TXB2 synthase at that dose; while at a dose of 300 mg/ml CP, the synthesis of TXB2 and 6-K were inhibited simultaneously (P less than 0.001). It showed that a larger dosage of CP, which could inhibited the synthesis of both TXA2 and PGI2, its mechanism of action needs further study.
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PMID:[Effects of Codonopsis pilosulae on the synthesis of thromboxane A2 and prostacyclin]. 220 15