Effect Of Suloctidil Research Articles

Effects of the antithrombotic drug suloctidil on low density lipoprotein processing and cholesterol metabolism in cultured human fibroblasts.

Human foetal lung fibroblasts were pretreated for 24 h with the antithrombotic drug, suloctidil (1 to 10 mumol/l), which induced a dose-dependent increase in LDL binding, uptake and degradation. At 10 mumol/l suloctidil, the respective increases in these parameters were 40%, 80% and 50%. The same treatment also resulted in increases of 1.5 to 2-fold in the synthesis of sterols, fatty acids and triacylglycerols from sodium acetate. In contrast, the esterification of cholesterol with oleic acid was specifically decreased by 35% by 24 h pretreatment of fibroblasts with 10 mumol/l suloctidil. A similar decrease of cholesterol esterification was observed in cholesterol-laden fibroblasts. It is suggested that these effects of suloctidil on LDL processing and cholesterol metabolism are related to the amphiphilic characteristics of the drug and to its calcium-blocking properties.

Effect of suloctidil on tomographically quantitated platelet accumulation in Dacron aortic grafts

Platelet deposition contributes to the thrombotic and embolic complications of prosthetic materials in man. To determine if the investigational platelet inhibitory drug suloctidil (200 mg 3 times daily) reduces platelet deposition on Dacron ® aortic grafts, a randomized, double-blind, crossover trial was conducted in 12 men with grafts that had been in place more than 9 months. Platelet deposition in the graft was assessed by quantitative analysis of planar images obtained at 24, 48 and 72 hours after injection of indium-111-labeled platelets. Also, a tomographic method of imaging and quantitating labeled platelet deposition in the graft was developed. Tomographic imaging was performed at 24 and 72 hours after platelet injection and was quantitated by a graft/ blood ratio that compared indium-111 platelet activity in summed 1.8-cm-thick transaxial tomographic slices of the aortic graft to indium-111 platelet activity in well-counted whole blood. Compared with placebo, suloctidil failed to decrease the tomographic graft/blood ratio at 24 hours (6.2 ± 1.3 vs 5.7 ± 0.8) and 72 hours (11.4 ± 2.9 vs 10.7 ±2.2). Similarly, the graft/blood ratio determined by planar imaging was not different between placebo and suloctidil therapy at 24 hours (1.7 ± 0.3 vs 1.6 ± 0.2), 48 hours (2.2 ± 0.4 vs 2.4 ± 0.4) or 72 hours (2.6 ± 0.5 vs 2.8 ± 0.5) after labeled platelet injection. Thus, suloctidil does not significantly reduce platelet deposition on chronically implanted Dacron grafts in humans.

Effect of suloctidil on rat liver.

The effect of suloctidil (120 mg/kg body weight PO for 3 weeks) on rat liver was investigated using biochemical and morphological methods: enzymatic activities characteristic of the main cellular compartments were used as biochemical markers of hepatocyte function and morphometry was applied to investigate morphological changes. No sign of hepatotoxicity was evidenced after suloctidil treatment (liver weight; cytochrome c oxidase; glucose 6-phosphatase; NADPH-cytochrome c reductase; D-amino acid oxidase; urate oxidase; fatty acid oxidation; peroxisomal number, volume and size distribution). Suloctidil increased catalase activity by 22% without morphologically detectable changes in the peroxisomes. After suloctidil treatment, slightly increased mitochondrial volume fraction and slightly decreased mitochondrial number were noted without significant changes in cytochrome c oxidase. Clofibrate, at the same dose, increased NADPH-cytochrome c reductase, catalase, acylCoA oxidase, mitochondrial and peroxisomal number and volume fraction, and decreased urate oxidase activity.

Effect of suloctidil on platelet function in patients with shortened platelet. Survival time

The effect of suloctidil (600 mg/day) on platelet survival time (PST) and plasma and urine betathromboglobulin (BTG) was studied in a double-blind, placebo-controlled six-week crossover trial in 13 patients with shortened PST (<110 hrs, exponential model). Mean PST after suloctidil (110.6 hrs) was significantly higher than in the placebo phase (94.5 hrs) (p=0.04). Mean plasma BTG was significantly lower during the suloctidil phase (42.8 ng/ml) compared with the placebo phase (65.8 ng/ml) (p=0.02), but there was no significant difference in urine BTG. These results suggest that suloctidil provides a platelet protective effect and therefore may be of benefit in reducing the frequency of platelet mediated thromboembolic events.

Effect of Suloctidil on dopaminergic transmission in various rat brain areas: Possible uses as drug for the elderly

Suloctidil is a drug used in the elderly endowed with a mechanism of action at neuronal level which has not been completely explored. The results of the present study indicate that acute treatment with suloctidil induces a decrease of serum prolactin levels and a decrease of 3,4-diidroxyphenylacetic acid concentrations in various rat brain areas. In addition, the repeated injection of small Suloctidil doses produces a down-regulation of dopaminergic receptors. These data suggest that Suloctidil has dopamino-mimetic properties in vivo. This pharmacological activity may be of importance in the clinical action of Suloctidil in the elderly.

Suloctidil-phospholipid interaction in bilayer membranes: Effects on lipid dynamics

The effects of suloctidil on the dynamic properties of dipalmitoyl- dl-α-phosphatidylcholine and dipalmitoyl- dl-α-phosphatidylcholine-phosphatidylserine in bilayer systems have been studied by fluorescence polarization using l,6-diphenyl-l,3,5-hexatriene as a fluorophore. A downward shift of the transition temperature of DPPC† in the presence of suloctidil and a general decrease in the fluorescence depolarization values suggest that suloctidil destabilizes the bilayer. These effects show a linear relationship with the amount of suloctidil present in the bilayer. Changes in the structure of the drug, pH of the buffer, lipid composition together with the measurement of the amount of suloctidil in the bilayer allow evaluation of the partition coefficient of the drug and suggests an electrostatic interaction between the drug and the acid phospholipid. The probable localization of suloctidil in the bilayer is discussed. These observations confirm the proposed mode of action of suloctidil deduced from its effect on Na +/K + ATPase activity and on membrane fluidity of rat brain synaptosomes.

Effect of suloctidil ∗ on Na +/K + ATPase activity and on membrane fluidity in rat brain synaptosomes

Effect of suloctidil ∗ on Na +/K + ATPase activity and on membrane fluidity in rat brain synaptosomes

In Vivo Effect of Suloctidil as an Antiplatelet Agent

The relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5-HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

Effect of suloctidil on bleeding time and in vivo platelet aggregation in rats

Effect of suloctidil on bleeding time and in vivo platelet aggregation in rats