Piretanide: A New Synthetic Fibrinolytic and Anti-Platelet Agent

1986 ◽  
Vol 56 (03) ◽  
pp. 360-363 ◽  
Author(s):  
I S Chohan
Keyword(s):  
Single Dose ◽  
Platelet Aggregation ◽  
Fibrinolytic Activity ◽  
Adenosine Diphosphate ◽  
Platelet Factor ◽  
Anti Platelet Agent ◽  
Effective Inhibition ◽  
Primary Platelet

SummaryPiretanide, 4-phenoxy-3-(l-pyrrolidinyl)-5-sulfamoyl benzoic acid, a potent diuretic, enhances endogenous plasma fibrinolytic activity after a single dose of 6 mg administered orally. Acceleration of fibrinolytic activity becomes manifest within 1 h, reaches its peak in 3 h and is associated with little change in fibrinogen, however, it is accompanied with diminished urokinase excretion initially. Piretanide does not cause lysis of fibrin in vitro in any concentration. Primary platelet aggregation, induced by adenosine-diphosphate, is inhibited by piretanide, in vivo. In in vitro experiments piretanide leads to effective inhibition of ADP-induced platelet aggregation with complete inhibition at 5 mM concentration. Piretanide, after ingestion of a single dose of 6 mg, causes highly significant decrease of platelet factor-4 release.

scholarly journals Furosemide and Platelet Functions

1977 ◽  
Author(s):  
I.S. Chohan ◽  
I. Singh ◽  
J. Vermvlen ◽  
M. Verstraete
Keyword(s):  
Platelet Aggregation ◽  
Ex Vivo ◽  
Metabolic Effects ◽  
Platelet Factor ◽  
Metabolic Products ◽  
Vitro Effect ◽  
Primary Platelet ◽  
Platelet Functions

Furosemide inhibits primary platelet aggregation by adenosine-5'-diphosphate and prolongs the latent period before Thrombofax- or collagen-induced platelet aggregation, both in vitro and ex vivo. Furosemide also inhibits the release of platelet factor 4 and 14C-serotonin. The inhibitory concentrations of furosemide in vitro range between 0.5 and 2.5 mM. The ex vivo effects were obtained after an intravenous injection of 40 mg furosemide.The furosemide concentrations required for ex vivo inhibition are hundred fold lower than those required for in vitro effect. This suggests in vivo metabolic effects of this drug, such as, calcium ions shifts, or action of other metabolic products of furosemide. In support of this concept platelet aggregation was found more disturbed six hours than 10 minutes after injection of the drug.

scholarly journals "Impotent" Platelets in Albinos With Prolonged Bleeding Times

Blood ◽  
1972 ◽  
Vol 39 (4) ◽  
pp. 490-499 ◽  
Author(s):  
Harold M. Maurer ◽  
James A. Wolff ◽  
Sue Buckingham ◽  
Arthur R. Spielvogel
Keyword(s):  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Bleeding Tendency ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time ◽  
Normal Platelet ◽  
Tryptophan Metabolites ◽  
History Of

Abstract Functional, biochemical, and morphologic platelet abnormalities are reported in four children with the syndrome of albinism, mild bleeding tendency, prolonged bleeding time, and normal platelet count. In these children, primary platelet aggregation with adenosine diphosphate occurred normally, but secondary aggregation was impaired. Collagen and norepinephrine produced almost no platelet aggregation. Platelet content of serotonin (5-HT) was markedly reduced, and uptake and retention of 5-HT by the platelets in vivo and in vitro was poor. In one child who was given a tryptophan load, urinary tryptophan metabolites were normal, suggesting that there was no evidence of a block in the 5-HT synthetic pathway in the gastrointestinal tract. Electron microscopy revealed an absence of densely osmophilic granules in 5-HT poor platelets. Platelets from other albinos with no history of bleeding contained normal amounts of 5-HT and densely osmophilic granules.

In Vitro and In Vivo Effects of Adrenaline and Phentolamine on Platelet Function

1978 ◽  
Vol 40 (02) ◽  
pp. 428-438 ◽  
Author(s):  
Oreste Ponari ◽  
Emilio Civardi ◽  
Alessandro Megha ◽  
Mario Pini ◽  
Raffaele Poti’ ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Threshold Concentration ◽  
Two Phase ◽  
Platelet Factor ◽  
Induce Platelet Aggregation ◽  
In Vivo Effects ◽  
In Vivo Administration

Summary In vitro and in vivo effects of adrenaline (ADR) on platelet aggregation, on platelet factor 3 (PF3) availability and on platelet factor 4 (PF4) release were studied in man. Inhibitory action of an alpha-blocker, phentolamine (PHEN) was investigated in the same conditions.The threshold concentration (TC) of ADR inducing the typical two-phase response in aggregation tests when added to platelet-rich plasma (PRP) varied in different pools of plasma, but always induced an evident PF4 release and increased PF3 availability. A further increase in both parameters was obtained with higher concentrations but without any significant dose/response correlation.Adding PHEN alone to PRP did not induce platelet aggregation or modify PF4 release induced by stirring, but it reduced PF3 availability. On the other hand, PHEN prevented the effects of ADR in different platelet tests, at appropriate concentrations.Intravenous infusion of ADR lowered the TC, and increased PF3 availability and PF4 release. In vivo administration of PHEN, in contrast, increased TC and reduced PF3 availability, while PF4 remained unchanged.

Prostaglandins and Platelet Aggregation in Vivo

1970 ◽  
Vol 23 (02) ◽  
pp. 286-292 ◽  
Author(s):  
J Kloeze
Keyword(s):  
Platelet Aggregation ◽  
Intravenous Injection ◽  
Adenosine Diphosphate ◽  
Causative Factor ◽  
Respiratory Arrest ◽  
Platelet Thrombi ◽  
Eventual Death ◽  
The Brain

SummaryProstaglandins E1 and ω-homo-E1 which were shown previously to inhibit adenosine diphosphate (ADP)-induced platelet aggregation in vitro have now been found to inhibit this process also in vivo. Both prostaglandins inhibit transient thrombocytopenia induced by intravenous injection of ADP; PGE1 increases also the LD 50 of ADP when injected in high amounts into young rats. In both cases platelet aggregation in vivo is the primary cause of the phenomena observed.The symptoms observed on overdosing ADP by intravenous injection are unconsciousness within 10-20 sec after completion of the injection immediately followed by respiratory arrest and eventual death of the animal, generally within 10 min. It seems that blocking of the supply of blood to the brain by platelet thrombi, which on histological examination were found to occlude blood vessels in different organs, is the most important causative factor of the symptoms observed.

scholarly journals Effect of propranolol on platelet function

Blood ◽  
1977 ◽  
Vol 49 (2) ◽  
pp. 185-196 ◽  
Author(s):  
BB Weksler ◽  
M Gillick ◽  
J Pink
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Direct Action ◽  
Blood Platelets ◽  
Adenosine Diphosphate ◽  
Ionophore A23187 ◽  
Atherosclerotic Vascular Disease ◽  
Clot Retraction

Abstract Excessive reactivity of blood platelets may contribute to atherosclerotic vascular disease. Hence drugs which alter platelet function may be protective. Prompted by findings that propranolol therapy normalized hyperactive platelet aggregation in patients with coronary artery disease, we studied propranolol in vitro to assess its action on platelets. At concentrations similar to those achieved in vivo (0.1–1 muM), propranolol raised the thresholds for aggregation of some normal paltelets by adenosine diphosphate (ADP). At higher concentrations (10-50 muM), propranolol abolished the second wave of platelet aggregation induced by ADP and epinephrine, and inhibited aggregation induced by collagen, thrombin, and the ionophore A23187. Propanolol blocked the release of 14C-serotonin from platelets, inhibited platelet adhesion to collagen, and interfered with clot retraction. Propranolol blocked ionophore-induced uptake of 45Ca by platelets. Inhibition appeared unrelated to beta-adrenergic blockage, as d(+) propranolol (which lacks beta-blocking activity) was equipotent with 1(-) propranolol. Moreover, practolol, a beta-blockading drug which is nonlipophilic, did not inhibit platelet function. These studies suggested that propranolol, like local anesthetics, decreased platelet responsiveness by a direct action on the platelet membrane, possibly by interfering with calcium availability. Modulation of platelet function by propranolol may occur at concentrations achieved at usual clinical doses of the drug.

Single-Dose Effect of Enteric-Coated Aspirin on Platelet Function and Thromboxane Generation in Middle-Aged Men

1993 ◽  
Vol 27 (4) ◽  
pp. 405-410 ◽  
Author(s):  
Hiroshi Mohri ◽  
Takao Ohkubo
Keyword(s):  
Single Dose ◽  
Platelet Aggregation ◽  
Bleeding Time ◽  
Adenine Nucleotides ◽  
Adenosine Diphosphate ◽  
Platelet Factor 4 ◽  
Middle Aged ◽  
Platelet Factor ◽  
Enteric Coated Aspirin ◽  
Enteric Coated

OBJECTIVE: To evaluate the effect of a single dose of enteric-coated aspirin (ECA) in three different dosages on platelet function and thromboxane generation in middle-aged men. DESIGN AND METHODS: In a nonblind, nonplacebo-controlled, crossover study, a single dose of ECA (50, 250, or 1000 mg) was given in a tablet form to a group of healthy, middle-aged men. Ten subjects, aged 50–67 years, volunteered to participate in this study. Platelet functions including bleeding time, platelet aggregation, adenine nucleotides, beta-thromboglobulin, platelet factor 4, thromboxane generation, and aspirin measurement were determined. RESULTS: Before ECA ingestion, the intracellular adenine nucleotides (adenosine triphosphate, adenosine diphosphate) were decreased, and both beta-thromboglobulin and platelet factor 4 were increased. These observations suggested that platelets were activated in vivo in middle-aged men. These findings returned to normal within 8 hours after the ingestion of ECA, and maintained normal for at least two days. Bleeding time was significantly prolonged at 8 and 24 hours compared with that before ingestion of ECA 1000 mg (p<0.05). The generation of platelet thromboxane was maximally inhibited by approximately 40 percent in the samples 8 hours after ECA ingestion. Abnormal values of adenine nucleotides, beta-thromboglobulin, and platelet factor 4 returned to normal within 8 hours. Arachidonic acid-induced platelet aggregation was inhibited compared with that before treatment (p<0.01) and the inhibitory effect was maintained for at least three days. Adenosine diphosphate- and epinephrine-induced aggregations were less inhibited than those induced by arachidonic acid. Inhibitory effects of ECA on platelet aggregation were dose dependent. CONCLUSIONS: Our study indicates that platelets are activated in middle-aged men and that a single dose of ECA 50 mg is safe and can inhibit thromboxane synthesis and platelet aggregation. These results suggest that a daily dose of ECA 50 mg may be useful for blocking platelet activation and preventing thrombosis.

Prostaglandins and Platelet Aggregation in Vivo

1970 ◽  
Vol 23 (02) ◽  
pp. 293-298 ◽  
Author(s):  
J Kloeze
Keyword(s):  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Blood Platelets ◽  
Adenosine Diphosphate ◽  
Primary Role ◽  
Electric Stimulus ◽  
Platelet Thrombi

SummaryIt was shown previously that prostaglandin E1 (PGE1) inhibits the aggregation of blood platelets in vitro whereas PGF1α does not; in vivo, PGE1 inhibits in rats the action of intravenously injected adenosine diphosphate. Locally administered PGE1 is found in the present experiment to inhibit in rats the formation and growth of platelet thrombi, induced by an electric stimulus in cortical veins. PGF1α appeared to be inactive.The morphology of platelet thrombi induced by an electric stimulus is shown. The probability of a primary role of erythrocytes in the formation of this type of thrombi is discussed.

Effect of Beta Blockers on Human Blood Plaletets in Vivo

1975 ◽  
Author(s):  
K. Zawilska ◽  
M. Komarnicki ◽  
B. Manka
Keyword(s):  
Platelet Aggregation ◽  
Human Blood ◽  
Beta Blockers ◽  
Normal Subjects ◽  
Platelet Factor ◽  
Induced Aggregation

ADP and collagen-induced platelet aggregations are diminished one hour after propanolol administration to normal subjects while adrenalin-induced aggregation and platelet factor 3 availability are not influenced. This effect of propanolol in vivo is very different from its in vitro action and is possibly related to the interaction adrenalin-ADP and collagen-ADP. Intermediary products of propanolol metabolism may also be involved in this effect.The administration of practololol to a second group of normal subjects had no effect on platelet aggregation and on platelet factor 3 availability.

Human Platelet Aggregation In Response To Multiple Agonists In Plasma Anticoagulated With Heparin

1981 ◽  
Author(s):  
H A Culliver ◽  
N G Ardlie
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Human Platelet Aggregation

The lowest concentrations at which epinephrine and vasopressin have been reported to interact positively in causing platelet aggregation in vitro are at least two orders of magnitude greater than the physiological concentrations of these hormones in blood. The aim of this study was to examine the interaction between several agonists of human platelet aggregation. The aggregating agents used were adenosine diphosphate (ADP), epinephrine, norepinephrine, 5-hydroxytryptamine and vasopressin. Platelet-rich plasma (PRP) was prepared from blood anticoagulated with minimal concentrations of heparin in an attempt to more closely reflect the in vivo situation.Aggregation caused by ADP was potentiated by epinephrine at a concentration exceeding the level obtained in circulating blood. When a third agonist (vasopressin) was used in combination with ADP and epinephrine, aggregation was enhanced at concentrations of vasopressin and epinephrine obtained in blood. When used as a fourth agonist norepinephrine and 5-hydroxytryptamine potentiated aggregation at physiological concentrations. The response to multiple agonists was greater in heparinized PRP than citrated PRP. Hirudin decreased the extent of aggregation in heparinized PRP caused by multiple agonists suggesting that thrombin may be involved.Since the concentrations of combined agonists required to induce in vitro platelet aggregation can be obtained in circulating blood these findings may explain why platelet activation occurs in certain pathological states.

scholarly journals Incorporation Of3H-Glycerol into Platelet Phospholipids During Platelet Aggregation

1977 ◽  
Author(s):  
R.A. Hutton ◽  
R.M. Hardisty
Keyword(s):  
Platelet Aggregation ◽  
Phosphatidyl Inositol ◽  
Direct Consequence ◽  
Adenosine Diphosphate ◽  
Secretory Process ◽  
Phospholipid Content ◽  
Platelet Phospholipid ◽  
Platelet Factor ◽  
Glycerol Uptake

In vitro incorporation of glycerol-2-3H into phospholipids of normal platelets was measured at rest and during platelet aggregation induced by adenosine diphosphate, epinephrine, collagen and ristocetin. Compared to the basal state, aggregating platelets showed a marked increase in total glycerol uptake, although total platelet phospholipid content was unchanged. The most striking change was an increase in the proportion of the radioactivity incorporated into the phosphatidyl inositol fraction (from 11% to 36% after 30 minutes incubation with epinephrine), this being largely at the expense of the phosphatidyl choline fraction which decreased from 46% to 30%. The extent of the glycerol uptake correlated well with the degree of platelet aggregation observed (p = 0.05 for adenosine diphosphate), but was not directly related to the speed of either aggregation or the release reaction. The rate of glycerol uptake paralleled the development of platelet factor 3 availability (PF3a) over the first 20-30 minutes of incubation, but thereafter, PF3a levelled off while glycerol uptake continued to rise for at least another 30 minutes. We conclude that the changes in platelet phospholipid turnover observed here during platelet aggregation, are of little direct consequence to the cells haemostatic functions. The increase in phosphatidyl inositol turnover may represent part of the cells’ response to membrane distortion or damage during the secretory process, as has been documented in other secretory processes.

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