piperidines has been researched along with sulotroban* in 3 studies
1 review(s) available for piperidines and sulotroban
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Pharmacology of the interaction between platelets and vessel wall.
The evaluation of agents inhibiting platelet function is difficult because, in addition to primary aggregation by thrombin, there are three amplification loops involving respectively arachidonate, ADP and PAF-acether (platelet activating factor). Each amplification loop seems eventually to act via a common pathway: the mobilization of calcium ions from the dense tubular system into the cytoplasm. Inhibition of this mobilization would prevent platelet aggregation by any agonist. This could be an ideal step with which to intervene pharmacologically. An intracellular increase in cAMP reduces cytoplasm calcium levels and therefore counteracts the effect of whatever agonist is used (Vermylen et al, 1982, 1983; Verstraete et al, 1985). Depending on the pro-aggregatory stimulus, the relative importance of a given pathway of platelet activation may shift. There is also uncertainty about which pathway of platelet activation predominates in a given clinical condition. The second problem relates to the pharmacology of the ideal drug for the inhibition of platelet function. It is very difficult to delineate the desired profile of such a drug considering the properties of the various compounds presently being studied (see Table 1). Prolongation of a shortened platelet survival in man was considered to be one of the key markers of an anti-aggregatory agent; this characteristic was found to be present after administration of sulphinpyrazone, clofibrate, ticlopidine, suloctidil, dipyridamole (in patients with artificial heart valves) and dipyridamole (in patients with venous thrombosis). The protective antithrombotic effect is most clearly demonstrated for aspirin; it is rather surprising that this drug does not prolong the shortened platelet survival in man, not even in those clinical conditions in which it effectively prevents thromboembolism. Topics: Animals; Aspirin; Blood Platelets; Blood Vessels; Dextrans; Diltiazem; Dipyridamole; Epoprostenol; Humans; Imidazoles; Ketanserin; Piperidines; Pyrazoles; Pyrazolones; Sulfinpyrazone; Sulfonamides; Thiophenes; Ticlopidine | 1986 |
2 other study(ies) available for piperidines and sulotroban
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Studies on the effects of agonists and antagonists on platelet shape change and platelet aggregation in whole blood.
The shape change that occurs when platelets are stimulated with an agonist can be quantitated by monitoring changes in their forward-scatter/side-scatter profile using a flow cytometer. Here we have stimulated platelets in citrated whole blood with several agonists and determined the time-course and extent of the shape change that occurs. In some experiments parallel investigations of shape change and aggregation were performed. Aggregation was measured by monitoring the fall in number of single platelets using a Whole Blood Platelet Counter. Some agents (ADP, PAF, U46619 and 5HT) produced a strong and rapid change in platelet forward-scatter/side-scatter that was maximal within 10 s. Others (A23187 and collagen) produced a strong but slower response. Adrenaline produced only a weak response that was also slow to develop, and PMA did not produce any response. The concentrations of each of ADP, PAF, U46619 and 5HT needed to induce a shape change were lower than those required for aggregation. Selective PAF, TXA2 and 5HT antagonists (WEB 2086, sulotroban and MCI-9042) clearly inhibited both the shape change and the aggregation induced by the appropriate agonist; in each case the effect of the antagonist was to move the dose-response curve to the right. These results are consistent with the shape change and aggregation brought about by each of these agonists being mediated via a single receptor. In contrast, a selective P2T purinoceptor antagonist (ARL 66096) markedly inhibited the aggregation induced by ADP but was found to have little or no effect on shape change. This is consistent with these platelet responses to ADP being mediated by different receptors, with P2T receptors mediating only the aggregation response. Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenosine Diphosphate; Adenosine Triphosphate; Azepines; Blood Platelets; Humans; In Vitro Techniques; Piperazines; Piperidines; Platelet Activating Factor; Platelet Aggregation; Platelet Aggregation Inhibitors; Prostaglandin Endoperoxides, Synthetic; Serotonin; Succinates; Sulfonamides; Thromboxane A2; Triazoles; Vasoconstrictor Agents | 1996 |
NIP-121 and cromakalim, potassium channel openers, preferentially suppress prostanoid-induced contraction of the guinea-pig isolated trachea.
We have investigated the relaxant effect of the potassium channel openers, NIP-121 and cromakalim, on spontaneous and spasmogen-induced tone in the isolated guinea-pig trachea. NIP-121 and cromakalim fully suppressed the spontaneous tone in a concentration-dependent manner and the maximal response was 89 and 97% of that to 1 mM aminophylline. The suppressant effect of NIP-121 (pD2 7.39) was 5 times stronger than that of cromakalim (pD2 6.69). Spontaneous tone was completely inhibited by the cyclooxygenase inhibitor, indomethacin, and partially inhibited by the thromboxane A2 (TXA2) antagonist, BM13177. In the presence of indomethacin, the contraction induced by prostaglandin (PG) F2 alpha and PGD2 was reversed by BM13177 to the same extent. NIP-121 and cromakalim reversed the contraction induced by PGF2 alpha, PGD2 and the TXA2 mimetic, U46619, and the effects were more potent than those observed on the contraction induced by leukotriene (LT) D4, LTC4, histamine and acetylcholine. The maximal relaxant responses (%) induced by NIP-121 and cromakalim were 97 and 96 for PGF2 alpha, 94 and 87 for PGD2, 94 and 93 for U46619, 69 and 69 for LTD4, 75 and 58 for LTC4, 73 and 61 for histamine and 1 and 16 for acetylcholine, respectively. The relaxant effect of NIP-121 on responses to these spasmogens (pD2 7.35 for PGF2 alpha, 7.40 for PGD2, 7.31 for U46619, 7.28 for LTD4, 7.09 for LTC4, and 7.15 for histamine) was about 10-20 times stronger than the effect of cromakalim (pD2 6.23 for PGF2 alpha, 6.04 for PGD2, 6.20 for U46619, 6.01 for LTD4, 5.82 for LTC4 and 5.88 for histamine).(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Animals; Arachidonic Acid; Benzopyrans; Cromakalim; Dinoprost; Glyburide; Guinea Pigs; Indomethacin; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Oxadiazoles; Piperidines; Potassium Channels; Prostaglandin D2; Prostaglandin Endoperoxides, Synthetic; Prostaglandins; Pyrroles; Sulfonamides; Trachea | 1991 |