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Effects of suloctidil on platelet survival time following cardiac valve replacement.

Platelet functions and blood clotting parameters were examined in 23 patients with a shortened platelet survival time after cardiac valve replacement. Treatment was given at random: for a first group antivitamin K with suloctidil and for the second group antivitamin K alone. Six weeks of treatment with antivitamin K alone did not induce any significant change in the platelet survival time, platelet retention or platelet factor 4 in plasma. In contrast, the shortened platelet survival time increased significantly after 6 weeks of treatment with suloctidil. Moreover the platelet retention and the amount of platelet factor 4 in plasma were significantly reduced, indicating that normalization of platelet survival is the result of decreased destruction, presumably at the level of the prosthetic surface. The clinical benefits expected from these results remain to be validated by a longer follow up period.

Acenocoumarol↗

[Effects of suloctidil on the central and peripheral nervous systems].

The effects of suloctidil (MY103) on the central (CNS) and peripheral nervous systems were investigated with single and consecutive administration. The general behavior in mice, awareness and motor activity were slightly depressed with the dose above 300 mg/kg, p.o. of MY 103. Soft stool was also marked in the dose above 100 mg/kg, p.o. in beagles and 1000 mg/kg, p.o. in mice. In beagles, vomiting was another syndrome with 100 and 300 mg/kg, p.o. of MY 103. Spontaneous motor activity was significantly decreased after MY 103 by p.o. administration in the dose above 100 mg/kg in mice and 300 mg/kg in rats. In sleep anesthesia studies, MY 103 and iproniazid did not potentiate the effect of a subthreshold dose of barbital, but those two drugs significantly prolonged the sleeping time of pentobarbital as chlorpromazine did. No anticonvulsive effect was observed with MY 103 in chemo- and electroshock seizure tests. My 103 of 300 mg/kg, p.o. significantly decreased the acetic acid induced writhing number, but no analgesic activity was found in the Haffner's method in mice. In the rotarod test, MY 103 of 30-300 mg/kg, p.o. inhibited the motor coordination dose-dependently. MY 103 antagonized the m-amphetamine group toxicity. A cataleptogenic effect was observed following the relatively high dose of MY 103 by an i.p. route. This effect was antagonized by atropine. The spinal reflexes in the immobilized cat, and spontaneous rabbit EEG were not affected by MY 103. The conditioned avoidance response (CAR) was also not changed with MY 103 in rats. In the isolated phrenic-nerve diaphragm preparation, 10(-4)M MY 103 irreversively inhibited the muscle twitches elicited by nerve and muscle stimulation, but suloctidil at 300 micrograms/kg, i.v., did not suppress the tibialis muscle twitches in vivo. In the consecutive administration study, MY 103 suppressed the CAR in rats and prolonged the thiopental-sleeping time in an administration period-related manner. These changes disappeared rapidly after drug withdrawal. Taking these evidences together, it can be concluded that MY 103 has little effect on the CNS with single administration, but the tendency to depress the CNS was observed after the repeated administration of MY 103.

Analgesics↗

[Chronic senile cerebrovascular insufficiency. Effects of suloctidil and pentoxifylline on erythrocyte deformability].

Red blood cell filtration, platelet aggregation, serum triglyceride and cholesterol levels were investigated in 15 patients with chronic cerebrovascular disease, 10 of whom treated with Suloctidil and 5 with pentoxifylline. The treatment was carried out in 90 days. Both pentoxifylline and Suloctidil produced a significant improvement of erythrocyte deformability and a decrease of platelet aggregation.

Cholesterol↗

Depletion of platelet amine storage granules by the antithrombotic agent, suloctidil.

Suloctidil, a compound with antithrombotic properties in animal models, causes depletion of human platelet serotonin stores during 1-5 hr incubation with platelet-rich plasma in vitro. This effect is not attended by leakage of cytoplasmic nucleotides or by alterations in cyclic AMP metabolism, malondialdehyde production or energy balance. 5HT uptake was also inhibited but uptake of adenine was not. 5HT released by suloctidil appeared in the supernatant as oxidation products, though the amine also accumulated when re-uptake was blocked by imipramine.

Adenine↗

Suloctidil: long-term trial in the aged. Study of microcirculation, viscosity, red cell deformability, fibrinolysis and lipid fractions.

15 aged patients with clinical and laboratory evidence of cerebrovascular insufficiency and/or myocardial sclerosis were given suloctidil (Locton) at the daily dose of 200 mg X 3, for 180 days, under the conditions of an open trial. Blood and plasma viscosity, red cell deformability, total lipids, cholesterol, triglycerides, fibrinolysis (plasminogen, antiplasmin, euglobulins with and without activator, fibrinogen), and capillaroscopic parameters in the small conjunctival vessels (artery, vein, and capillary diameter, appearance of collaterals, red cell aggregation and flow homogeneity) were evaluated. After 30 days of treatment and particularly at the end of the trial a significant improvement of almost all these parameters was observed. Tolerance was always excellent.

Aged↗

Effect of suloctidil on cerebral circulation patterns of conscious rabbits.

Suloctidil (SUL) produces calcium antagonistic and antispasmodic effects on peripheral and pial arteries. The present studies were performed with the aim of evaluating the action of SUL on cerebral blood flow (CBF), which was taken as an index for evaluating the cerebral circulation. The drug was administered by rapid intravenous injection to groups of unanaesthetized rabbits at doses of 100-200 micrograms/kg and by intravenous infusion at doses of 10-20 micrograms/kg/min. In other experiments, SUL was chronically administered p.o. to normal rabbits and to rabbits receiving Kritchevsky's atherogenic diet; the daily dose of the drug was about 16 mg/kg. Cerebral blood flow and its compartmental distribution were determined in unanaesthetized animals by the intracarotid 133Xe clearance method. The data demonstrate that the atherogenic diet brings about a significant impairment of CBF; SUL is inactive in normal rabbits, while in the atherosclerotic rabbits it induces a pronounced increase in cerebral blood flow in the grey matter and an enhancement of the corresponding circulatory compartment. These changes are less evident in the white matter.

Anesthesia↗

[Protective effect of suloctidil against cerebral hypoxia (author's transl)].

The protective effect of suloctidil [MY 103, erythro-1-(4-isopropylthiophenyl)-2-n-octylaminopropanol] against cerebral hypoxia was investigated in terms of survival time under normobaric hypoxia (96% N2 + 4% O2 gas mixture) in mice and evoked potential in prepyriform cortex of guinea pig in vitro. In a hypoxic condition, the pretreatment with MY 103 (3.0-12.5 mg/kg, i.p.) resulted in a marked and dose-dependent prolongation of survival time of mice without any adverse effect. The prolongation of survival time was statistically significant at doses over 6.3 mg/kg. The amplitude of evoked potential to electrical stimulation of olfactory tract in the brain slice was consistently and reversibly suppressed by the perfusion with low oxygen Ringer's solution containing about 45% O2 or normal Ringer's solution. This amplitude reduction after 6 minutes exposure to hypoxic perfusate, was consistently reproducible in the same preparation. Preincubation of brain slices in normal Ringer's solution containing 10(-7)-10(-6) g/ml MY 103 for 15 min, however, effectively prevented the hypoxic reduction of the amplitude of evoked potentials to 30-50% of the control experiments. The above data indicate that MY 103 exerts its anti-anoxic effect presumably through modified metabolic processes such as active oxygen or glucose uptake by the brain.

Animals↗

[Effect of suloctidil on cerebral venous outflow in the dog (author's transl)].

The effects of intravenous administration of suloctidil [erythro-1-(4-isopropylthiophenyl)-2-n-octylamino-propanol], (MY 103) on cerebral venous outflow (VOF), blood gases, cerebral metabolic rate of oxygen (CMRO2) and other hemodynamic parameters were studied and effects compared to those of cinnarizine and papaverine, in gallamine immobilized dogs. MY103 and papaverine at doses 0.1-1.0 mg/kg, i.v. caused significant increases in VOF by 6.1-38.3% and 12.1-26.1% respectively. The changes in VOF persisted for 1.4 min and 0.5 min in mean following 1.0 mg/kg, i.v. of MY103 and papaverine, respectively. Cinnarizine also increased VOF by 10.0 and 18.7% at doses 0.3 and 1.0 mg/kg i.v. The duration of VOF changes by cinnarizine 1.0 mg/kg, i.v., 2.4 min (mean), was no longer than the duration seen with the same dose of MY103 or papaverine. Mean blood pressure (MBP) decreased dose dependently with these drugs and consequently the cerebral vascular resistance (CVR) decreased 8.6-40.2% with MY103, 13.6-25.0% with cinnarizine and 16.1-39.5% with papaverine administration, respectively. MY103 and papaverine at a dose of 1.0 mg/kg i.v. did not affect pH, Pco2 and Po2 in arterial blood, but these two drugs did show a tendency to lower Pco2 and elevate Po2 in cerebral venous blood. CMRO2 was not significantly affected by MY103 or papaverine. It is suggested that cerebral vasodilation may be the mechanism for VOF increase following MY103 administration.

Animals↗

[Hemorrheological survey in a group with arteriosclerotic vascular disease treated with suloctidil].

In 17 patients affected by atherosclerotic vascular disease and showing in basal conditions a hyperviscosity state, we have monitored the main hemorheological determinants during treatment with Suloctidil. At the end of treatment carried out for 5 months the results showed that erythrocyte filterability was the only hemorheological determinant influenced. The possible causes of this action are therefore considered.

Aged↗

Antiplatelet and antithrombogenic effects of suloctidil.

Platelet aggregation induced in mice or rats by i.v. ADP can be antagonized by oral administration of suloctidil. This effect on platelet behaviour appears to be sufficient to reduce the rate of thrombotic occlusion of the femoral artery in the dog and to protect the rat against occurrence of thrombophlebitis.

Adenosine Diphosphate↗

Effects of suloctidil on lipid metabolism in experimental animals.

A novel potent vasoactive agent, 1-(4-isopropyl-thiophenyl)-2-n-octylaminopropanol (suloctidil, Sulocton), lowers excess of plasma cholesterol and tends to normalize the plasma hyperbetalipoproteinemia of Rhesus monkeys fed a high-cholesterol, high-fat diet. The drug shows an inhibitory effect on the cholesterol biosynthesis in rat liver homogenates.

Animals↗