Inhibitors of platelet signal transduction as anti-aggregatory drugs

Expert Opinion on Investigational Drugs

Volumn 10, Issue 5, 2001, Pages 865-890

  Geiger, J ^a  

^a UNIVERSITY HOSPITAL WÜRZBURG   (Germany)

Author keywords

Antiplatelet drugs; Cyclooxygenase inhibitor; Endothelial factors; Phosphodiesterase inhibitor; Thromboxane synthase inhibitor

Indexed keywords

ACADESIN; ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; ARACHIDONIC ACID; ATAPROST; BERAPROST; CD39 ANTIGEN; CIPROSTENE; CYCLIC AMP; CYCLIC GMP; CYCLIC NUCLEOTIDE; CYCLOOXYGENASE 1; HEPARIN; ILOPROST; MEMBRANE RECEPTOR; NITROUS OXIDE; NUCLEOTIDASE; PHOSPHODIESTERASE; PHOSPHODIESTERASE INHIBITOR; PROSTACYCLIN; PROSTACYCLIN DERIVATIVE; PROSTAGLANDIN E1; RECEPTOR BLOCKING AGENT; TAPROSTENE; THROMBOCYTE SLOWING FACTOR; THROMBOXANE; THROMBOXANE PRECURSOR; THROMBOXANE RECEPTOR; THROMBOXANE SYNTHASE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARACHIDONIC ACID METABOLISM; BLOOD LEVEL; CARDIOVASCULAR DISEASE; CLINICAL RESEARCH; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG COMBINATION; DRUG EFFICACY; DRUG METABOLISM; DRUG POTENCY; DRUG POTENTIATION; DRUG SPECIFICITY; DRUG TARGETING; ENDOTHELIUM; ENZYME INHIBITION; HUMAN; IN VIVO STUDY; METABOLISM; MOLECULAR MIMICRY; NONHUMAN; PHASE 3 CLINICAL TRIAL; PRECURSOR; RAT; REVIEW; SIGNAL TRANSDUCTION; SMOOTH MUSCLE RELAXATION; THROMBOCYTE; THROMBOCYTE ACTIVATION; THROMBOCYTE AGGREGATION; VASCULAR SMOOTH MUSCLE; VASODILATATION;

ANIMALS; BLOOD PLATELETS; CYCLIC AMP-DEPENDENT PROTEIN KINASES; CYCLIC GMP-DEPENDENT PROTEIN KINASES; CYCLOOXYGENASE INHIBITORS; DRUG THERAPY, COMBINATION; EICOSANOIDS; HUMANS; NITRIC OXIDE; PHOSPHODIESTERASE INHIBITORS; PLATELET AGGREGATION INHIBITORS; SIGNAL TRANSDUCTION; THROMBOXANE-A SYNTHASE;

EID: 0035011368     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.10.5.865     Document Type: Review

References (206)

1. Anti-aggregatory drugs: I. Platelet receptor antagonists
2. Molecular mechanism of platelet activation
3. The role of heterotrimeric G proteins in platelet activation
4. Pharmacological receptors on blood platelets
5. Calcium signaling in human platelets
6. Studies on the role of cyclic AMP in platelet function
7. The cloned platelet thrombin receptor couples to at least two distinct effectors to stimulate phosphoinositide hydrolysis and inhibit adenylyl cyclase
8. Signal transduction pathways mediated by glycoprotein Ia/IIa in human platelets: Comparison with those of glycoprotein VI
9. Collagen receptor signaling in platelets and megakaryocytes
10. 2 receptor-stimulated phosphoinositide hydrolysis in isolated platelet membranes: Involvement of phosphoinositide-specific phospholipase C-β and GTP-binding Gq
11. Platelet signal transduction pathways: Could we organize them into a 'hierarchy'?
12. Platelet activation
13. The anti-aggregating properties of vascular endothelium interactions between prostacyclin and nitric-oxide
14. Mechanisms of disease - Regulatory functions of the vascular endothelium
15. The role of nitric oxide and other endothelium-derived vasoactive substances in vascular diseases
16. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine
17. Nitric oxide and its role in the cardiovascular system
18. Synergistic inhibition of platelet aggregation by endothelium-derived relaxing factor and prostacyclin
19. The pathogenesis of atherosclerosis - A perspective for the 1990's
20. Platelet-endothelium interactions
21. The nitric oxide and cGMP signal-transduction pathway
22. Platelet arachidonic acid metabolism and eicosanoid receptors
23. Nitric oxide-physiology, pathophysiology and pharmacology
24. Regulation of blood platelet function by cyclic nucleotides
25. The regulation of platelet function by protein kinases
26. Endothelial cell-dependent phosphorylation of platelet protein mediated by cAMP- and cGMP-elevating agents
27. Characterization of Sp-5,6-dichlorobenzimidazolriboside 3′ 5′ -monophosphorothioate (Sp-5,6-DCI-cBiMPS) as potent and specific activator of cAMP-dependent protein kinase in cell extracts and intact cells
28. Analysis of the functional role of cGMP-dependent protein kinase in intact human platelets using a specific activator 8-para-chlorophenylthio-cGMP
29. Megakaryocyte hyperplasia and enhanced agonist-induced platelet activation in vasodilator-stimulated phosphoprotein knockout mice
30. Role of cGMP and cGMP-dependent protein kinase in nitrovasodilator inhibition of agonist-evoked calcium elevation in human platelets
31. Regulation of calcium mobilization and calcium entry in human platelets by cyclic nucleotide-elevating and endothelium-derived factors
32. The effects of nitric oxide (NO) on platelet membrane receptor expression during activation with human α-thrombin
33. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
34. Endothelium derived relaxing factor inhibits in vitro platelet aggregation
35. Endothelium-derived relaxing factor inhibits platelet aggregation in human whole blood in vitro and in the rat in vivo
36. Comparative effects of nitroprusside and nitroglycerin on platelet aggregation in patients with heart failure
37. The effects of organic nitrates on prostacyclin biosynthesis and platelet function in humans
38. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: Evidence for the involvement of S-nitrosothiols as active intermediates
39. Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase
40. Effects of sodium nitroprusside and other smooth muscle relaxants on cyclic GMP formation in smooth muscle and platelets
41. Sodium nitroprusside and other smooth muscle-relaxants increase cyclic GMP levels in rat ductus deferens
42. Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine
43. Inhibition of platelet activating factor-induced platelet aggregation by molsidomin, SIN-1 and nitrates in vitro and ex vivo
44. Organic nitrates: Direct antiplatelet effects and synergism with prostacyclin
45. Inhibition of platelet function by organic nitrate vasodilators
46. Mechanisms of nitrate-induced vasodilation and tolerance on a biochemical base
47. Sustained antiplatelet properties of nitroglycerin during hemodynamic tolerance in rats
48. Biotransformation of glyceryl trinitrate by blood platelets as compared to vascular smooth muscle cells
49. Antithrombotic properties of a novel sydnonimine derivative
50. Inhibition of platelet aggregation and stimulation of guanylate cyclase by an antianginal agent, molsidomine and metabolites
51. 2+ and on aggregation of human platelets
52. S-Nitrosylation of proteins with nitric oxide: Synthesis and characterization of biologically active compounds
53. Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide
54. S-nitrosoglutathione inhibits platelet activation and deposition in coronary artery saphenous vein grafts in vitro and in vivo
55. S-nitrosoglutathione reduces the rate of embolization in humans
56. Chemical mechanisms underlying the vasodilator and platelet anti-aggregating properties of S-nitroso-N-acetyl-DL-penicillamine and S-nitrosoglutathione
57. 2 synthesis in human blood platelets
58. Evidence for a cyclic GMP-independent mechanism in the anti-platelet action of S-nitrosoglutathione
59. Systemic effects of S-nitrosoglutathione in the human following intravenous infusion
60. FK409, a novel vasodilator isolated from the acid-treated fermentation broth of Streptomyces griseospereus. I. Taxonomy, fermentation, isolation and physico-chemical and biological characteristics
61. Spontaneous nitric oxide release accounts for the potent pharmacological actions of FK409
62. Comparison of antiplatelet effects of FK409, a spontaneous nitric oxide releaser, with those of TRK-100, a prostacyclin analogue
63. Antiplatelet activities of FK409, a new spontaneous NO releaser
64. Release of nitric oxide from donors with known half-life: A mathematical model for calculating nitric oxide concentrations in aerobic solutions
65. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation
66. Effects of prostacyclin (PGX) on cyclin AMP concentration in human platelets
67. 2 on platelet aggregation in different species
68. 2 receptor
69. Model of prostaglandin-regulated cyclic AMP metabolism in intact platelets: Examination of time-dependent effects on adenylate cyclase and phosphodiesterase activities
70. 2 receptors in human platelets
71. 2 on human platelets
72. 2 on platelets
73. 2 on human platelets
74. 3H]adenosine binding in relation to adenylate cyclase activity
75. Pharmacology of adenosine A2A receptors
76. Prostacyclin-analogs
77. Novel antithrombotic drugs in development
78. Pharmacokinetics and pharmacodynamics of radio-labelled iloprost in elderly volunteers
79. 1, on human platelet function
80. Antithrombotic profile of iloprost in experimental models of in vivo platelet aggregation and thrombosis
81. Iloprost -A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in peripheral vascular disease, myocardial ischaemia and extracorporeal circulation procedures
82. Trial of iloprost versus aspirin treatment for critical limb ischaemia of thromboangiitis obliterans
83. 2 analogue) in the atherosclerotic rabbit artery after angioplasty
84. Platelet-aggregation inhibition and hemodynamic effects of beraprost sodium, a new oral prostacyclin derivative: A study in healthy male subjects
85. A dose-effect study of beraprost sodium in intermittent claudication
86. 2 analog, on parameters of hemostasis, fibrinolysis and myocardial ischemia in patients with exertional angina
87. 2 analogue on vascular endothelial function and platelet aggregation in patients with NIDDM
88. Studies on antioplatelet effect of OP-41483, a prostacyclin analog, in experimental animals. I. Effect on platelet function and thrombosis
89. Clinical studies on the vasodilating and anti-platelet effects of OP-41483, a prostacyclin derivative
90. 2 analog in healthy volunteers
91. Activation of thromboxane and prostacylcin receptors elicits opposing effects on vascular smooth muscle cell growth and mitogen-activated protein kinase signaling cascades
92. In vitro analysis of synergistic effects of fibrinolytic agents and prostacyclin analogues
93. In vivo studies with the stabilized epoprostenol analogue taprostene
94. The effect of taprostene in patients with acute myocardial infarction treated with thrombolytic therapy: Results of the START study. Saruplase taprostene acute reocclusion trial
95. 1 and iloprost vs. saline
96. Rationale and methodology of the ICAI study, a randomised clinical trial of alprostadil in the treatment of chronic critical leg ischemia
97. 1 and iv pentoxyfylline in patients with arterial occlusive disease of fontaine stage IIb: A multicenter, randomized comparative study
98. Effects of adenosine on levels of adenosine cyclic 3′5′-monophosphate in human blood platelets in relation to adenosine incorporation and platelet aggregation
99. Dipyridamole
100. Acadesine (AICA riboside) inhibits platelet aggregation in human whole blood
101. Adenosine-mediated inhibition of platelet aggregation by acadesine. A novel antithrombotic mechanism in vitro and in vivo
102. Acadesine reduces the frequency of coronary artery reocclusion following rt-PA induced thrombolysis in the dog
103. Multiple cyclic nucleotide phosphodiesterases
104. Human blood platelet 3′,5′-cyclic nucleotide phosphodiesterase. Isolation of low Km and high Km phosphodiesterase
105. Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function and the contractile responses of trabeculae carneae and aortic ring in vitro
106. Differential modulation of tissue function and therapeutic potential of selective inhibitors of cyclic nucleotide phosphodiesterase isoenzymes
107. Cyclic nucleotide phosphodiesterases: Functional implications of multiple isoforms
108. Cyclic GMP phosphodiesterase-5: Target of sildenafil
109. Effect of cilostazol on platelet aggregation and experimental thrombosis
110. Antiplatelet therapy using cilostazol, a specific PDE3 inhibitor
111. Pharmacological treatment of intimal hyperplasia after metallic stent placement in the peripheral arteries
112. Potentiation of anti-platelet aggregating activity of cilostazol with vascular endothelial cells
113. Inhibition of shear stress-induced platelet aggregation by cilostazol, a specific inhibitor of cGMP-inhibited phosphodiesterase, in vitro and ex vivo
114. Clinical evaluation on combined administration of oral prostacyclin anologue beraprost and phosphodiesterase inhibitor cilostazol
115. A randomized trial of aspirin versus cilostazol therapy after successful coronary stent implantation
116. A new pharmacological treatment for intermittent claudication: Results of a randomized, multicenter trial
117. Dipyridamole alone or combined with low dose acetylsalicylic acid inhibits platelet aggregation in human whole blood ex vivo
118. European Stroke Prevention Study 2: Efficacy and safety data
119. European stroke prevention study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke
120. Bleeding complications in secondary stroke prevention by antiplatelet therapy: A benefit-risk analysis
121. Inositol lipids, phosphatidate and diacylglycerol share stearoylarochidonoylglycerol as a common backbone in thrombin-stimulated human platelets
122. Prostaglandin endoperoxide synthase: Structure and catalysis
123. Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression and gene chromosomal location
124. Structure of the mitogen-inducible TIS-10 gene and demonstration that the TIS-10 encoded protein is a functional prostaglandin G/H synthase
125. 2 production
126. The eicosanoids and their biochemical mechanism of action
127. Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides
128. Acetylation of prostaglandin synthase by aspirin
129. PGH synthase isoenzyme selectivity: The potential for safer nonsteroidal antiinflammatory drugs
130. Differential inhibition of human prostaglandin endoperoxide H synthases-1 and -2 by nonsteroidal anti-inflammatory drugs
131. Effect of KBT-3022, a new diphenylthiazole derivative, on platelet functions
132. The mechanism of action of KBT-3022, a new antiplatelet agent
133. Antithrombotic effects in a rat model of aspirin-insensitive arterial thrombosis of desethyl KBT-3022, the main active metabolite of a new antiplatelet agent, KBT-3022
134. Anti-thrombotic activity of KBT-3022, in experimental models of thrombosis
135. Triflusal
136. Inhibition of cyclooxygenase-2 expression by 4-trifluoromethyl derivatives of salicylate, trifusal and its deacetylated metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid
137. Triflusal vs. aspirin on the inhibition of human platelet and vascular cyclooxygenase
138. Protective effect of triflusal against acute myocardial infarction in patients with unstable angina: Results of a Spanish multicenter trial
139. Triflusal in the treatment of patients with chronic peripheral arteriopathy: Multicentre double-blind clinical study vs. placebo
140. Influence of triflusal on platelet activation after coronary artery bypass graft
141. Differential suppression of thromboxane biosynthesis by indobufen and aspirin in patients with unstable angina
142. A prostacyclin sparing effect of indobufen vs. aspirin
143. Reduction by indobufen of neutrophil activation in peripheral arterial occlusive disease
144. Indobufen compared with aspirin and dipyridamole on graft patency after coronary by pass surgery: Results of a combined analysis
145. A randomized trial comparing ticlopidin hydrochloride with indobufen for the prevention of stroke in high-risk patients TISS Study (Ticlopidin Indobufen Stroke Study)
146. Indobufen versus warfarin in the secondary prevention of major vascular events in nonrheumatic atrial fibrillation
147. Thromboembolic complications and pharmacological prophylaxis in orthopaedic surgery
148. Effects of indobufen and pentoxifylline on walking capacity and hemostasis in patients with intermittent claudication: Results of six months of treatment
149. Antiplatelet agents based on cyclooxygenase inhibition without ulcerogenesis. Evaluation and synthesis of 4,5-bis-(4-methoxy phenyl)-2-substituted-thiazoles
150. Isolation and characterization of thromboxane synthase from human platelets as cytochrome P450 enzyme
151. Role of proaggregatory and anti-aggregatory prostaglandins in hemostasis
152. Platelet interaction with vascular smooth muscle in synthesis of prostacyclin
153. Thromboxane synthase inhibitors (TXSI). Dosing, synthesis and evaluation of a novel series of (t)-pyridylalkenoic acids
154. Spectral studies on structure-activity relationships of thromboxane synthase inhibitors
155. 2) synthase inhibitor: Modulation of the antiplatelet action and prostanoid rings
156. 2 synthetase inhibitor on ventricular arrythmias induced by coronary artery occlusion in rats
157. Effect of CV 4151 on platelet aggregation (whole blood and PRP) in patients with cerebrovascular disease
158. Pharmacokinetic and pharmacodynamic studies following single and multiple doses of rolafagrel, a novel inhibitor of thromboxane synthase, in normal volunteers
159. A Phase I dose-ranging safety and pharmacokinetics study of a novel oral thromboxane synthase inhibitor, FCE 22,178
160. Design of an antithrombotic-antihypertensive agent (Wy 27569). Synthesis and evaluation of a series of 2-heteroaryl-substituted dihydropyridines
161. A biological method for studying the interaction between platelets and vascular endothelium
162. The mechanism of anti-thrombotic, thrombolytic and fibrinolytic actions of camonagrel - A new thromboxane synthase inhibitor
163. Superiority of platelet integrin GPIIb/IIIa receptor antagonist over aspirin in preventing cyclic flow reductions in the guinea pig middle cerebral artery
164. Effect of various antiplatelet agents on acute arterial thrombosis in the rat
165. Inhibition of platelet function by an aspirin-insensitive endothelial cell ADPase
166. Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation
167. Nucleotides and cd39: Principal modulatory players in hemostasis and thrombosis
168. Inhibition of platelet function by recombinant soluble ecto-ADPase/CD39
169. Antiplatelet and antithrombotic activities of NQ301, 2-chloro-3-(4-acetophenyl)-amino-1,4- naphthoquinone
170. Studies on the antithrombotic and antiplatelet activities of NQ304, a newly synthesised naphthoquinone derivative
171. Nitric oxide donors increase mucus gel thickness in rat stomach
172. The development of gastrointestinal-sparing nonsteroidal anti- inflammatory drugs
173. In vitro study of the anti-aggregating activity of two nitroderivatives of acetylsalicylic acid
174. 2 production
175. Conversion of a polysaccharide to nitric oxide-releasing form dual-mechanism anticoagulant activity of diazeniumdiolated heparin
176. Unique antiplatelet effects of a novel S-nitrosoderivative of a recombinant fragment of von Willebrand factor, AR545C: In vitro and ex vivo inhibition of platelet function
177. 2 synthase inhibition alone and in combination: Comparison of anti-aggregatory efficacy in human platelets
178. Pharmacological manipulation of the thromboxane pathway in blood platelets
179. 2 synthase and blockade of coronary thrombosis
180. R68070, a combined thromboxane/endoperoxide receptor antagonist and thromboxane synthase inhibitor, inhibits human platelet activation in vitro an in vivo: A comparison with aspirin
181. 2 synthetase and receptors enhances thrombolysis and delays reocclusion in canine coronary arteries
182. The effect of combined administration of ridogrel and ketanserin in patients with intermittent claudication
183. Thromboxane synthase inhibitors suppress more effectively the aggregation of thromboxane receptor-desensitized than of normal platelets: Role of adenylyl cyclase up-regulation
184. 2 on endothelial cell proliferation: Effect of specific receptor antagonists
185. 2/prostaglandin endoperoxide receptor antagonist, versus aspirin as adjunct to thrombolysis in myocardial infraction. The Ridogrel Versus Aspirin Patency Trial (RAPT)
186. 2 receptor antagonist in human platelets
187. 2 production
188. 2-synthase inhibitor and -receptor antagonist, on human platelets
189. 2 production in vivo
190. Effect of picotamide on the calcium mobilization and phospholipase C activation in human platelets
191. 2 antagonism
192. Effects of picotamide, an antiplatelet agent, on cardiovascular events in 438 claudicant patients with diabetes: A retrospective analysis of the ADEP study
193. Safety and efficacy of picotamide, a dual anti-thromboxane agent, in patients with thrombocytosis and a previous thromboembolic event: A 1-year observational study
194. Anti-aggregatory effects of picotamide in long-term treatment: A 2-year, double blind placebo controlled trial
195. Long-term safety and efficacy of picotamide, a dual-action antithromboxane agent, in diabetic patients with carotid atherosclerosis: A 6-year follow-up study
196. Effect of aspirin or picotamide, an antithromboxane agent, in combination with low-intensity oral anticoagulation in patients with acute myocardial infarction: A controlled randomized pilot trial
197. Pharmacological profile of G619, a new platelet aggregation inhibitor
198. 2 receptor antagonists and synthase inhibitors
199. A new anti-platelet drug, E5510, has multiple suppressive sites during receptor-mediated signal transduction in human platelets
200. Mechanism of satigrel (E5510), a new anti-platelet drug, in inhibiting human platelet aggregation. Selectivity and potency against prostaglandin H synthase isozyme activities and phosphodiesterase isoform activities
201. Inhibitory effects of a novel antiplatelet agent, E5510, on collagen-induced platelet-derived growth factor release and aggregation of human platelets in vitro
202. A randomized trial of E5510 versus aspirin in patients with transient ischemic attacks
203. Antiplatelet Synergistic effect of ridogrel, a combined thromboxane receptor antagonist and thromboxane synthase inhibitor and UDCG-212, a cAMP phosphodiesterase inhibitor
204. A comparative evaluation of thromboxane receptor blockade, thromboxane synthase inhibition and both in animal models of arterial thrombosis
205. Preliminary clinical studies with thromboxane synthase inhibitors and thromboxane receptor blockers. A review
206. Antiplatelet agents in stroke prevention - Combination therapy: Present and future