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At least 19 recordsLinked to original sources

PubMed1983

[Antigenicity of suloctidil].

Studies on antigenicity of suloctidil were performed on ASA, Schultz-Dale reaction, PCA and PHA in guinea pigs. Two sensitizing procedures were enforced. One was performed by means of treatment of suloctidil (p. o. and i. p.) and the other was done by means of injection of suloctidil, suloctidil-BSA-mixture and suloctidil-BSA-conjugate emulsified with FCA. Guinea pigs treated with suloctidil by oral or intraperitoneal administration showed no ASA, Schultz-Dale reaction, PCA and PHA by the challenge of suloctidil. The animals treated with suloctidil-BSA-conjugate only evoked severe anaphylactic reaction to challenge of suloctidil-OVA-conjugate. Guinea pigs treated with suloctidil and suloctidil-BSA-mixture showed no anaphylactic reaction to challenge of suloctidil, suloctidil-OVA-mixture and suloctidil-OVA-conjugate. The animals sensitized with suloctidil-BSA-conjugate showed no anaphylactic reaction to challenge of suloctidil and suloctidil-OVA-mixture. Therefore, it is concluded that suloctidil does not have any antigenicity.

Anaphylaxis↗

PubMed1986

In vitro vasorelaxing activity of suloctidil.

The vasorelaxing effect of suloctidil was evaluated in isolated rat and rabbit aorta and in isolated rabbit mesenteric and saphenous artery. Suloctidil inhibited contractions induced by increasing extracellular calcium in depolarized arteries, mainly in a competitive way. In the rat aorta, the pA2 value was 7.50 for suloctidil, while pA2 values of 9.96, 7.90 and 8.10 were obtained for nifedipine, cinnarizine and verapamil, respectively. Suloctidil more potently inhibited calcium-induced contractions in small arteries (mesenteric and saphenous artery), than in the aorta. Suloctidil also reduced the tonic component of the responses to norepinephrine. In contrast to the effects on calcium-induced contractions, the effects of suloctidil on norepinephrine-induced responses was mainly noncompetitive. In addition, and unlike cinnarizine and verapamil, high concentration of suloctidil also reduced the phasic component of contractile responses to norepinephrine. Furthermore, unlike nifedipine, verapamil, diltiazem and cinnarizine, suloctidil was devoid of a negative inotropic effect in spontaneously beating guinea-pig atria. In conclusion, suloctidil behaves as a Ca2+-channel blocker in arteries and displays an additional mode of action that could include receptor-operated Ca2+-channels or an intracellular site of action. In addition, suloctidil was found to affect small arteries more than the aorta, and not to affect the atria.

Animals↗

PubMed1983

[Effect of suloctidil in the protection of the cerebral function].

It has been demonstrated that suloctidil [erythro-1-(4-isopropylthiophenyl)-2-n-octylaminopropanol] has a protective effect against cerebral hypoxia to elongate the survival time of mice subjected to normobaric hypoxia (96% N2 + 4% O2 gas mixture). In this study, further experiments were done to elucidate the mechanism of protection against cerebral hypoxia with a variety of experimental models. Pretreatment (30 min) with suloctidil (12.5-50 mg/kg, i.p.) increased the number of gasping in the decapitated head of mouse as a complete ischemic model. Pyrithioxine (25, 50 mg/kg, i.p.) or cinnarizine (50, 100 mg/kg, i.p.) did not increase the gasping number. In the histotoxic anoxia with KCN (4 mg/kg, i.v.) in mice, suloctidil showed 30.8% and 46.2% survival rates at the doses of 25 and 50 mg/kg, i.p., respectively. Concerning this result, it has been revealed that suloctidil did not have any methemoglobin formation liability in rats (unpublished). Pyrithioxine did not show such protection following the injection of 12.5-50 mg/kg, i.p.. Suloctidil (3.0-50 mg/kg, i.p.) and pyrithioxine (3.0, 10 mg/kg, i.p.) significantly prolonged the survival time of mice subjected to hypobaric hypoxia (210 mmHg). In this cerebral hypoxia model, suloctidil kept glucose at a significantly higher level and lactate at a lower level in the brain of mice that were administered this drug than the control group. ATP was kept at higher level after suloctidil than the control under hypobaric hypoxia. Taking these evidences together, it can be concluded that suloctidil exerts its cerebral anti-hypoxic effect through cerebral glucose metabolism coupled with oxidative phosphorylation to yield the high energy substance ATP in a variety of models tested in this study. The fact obtained in this study, together with increase in cerebral blood flow by suloctidil, may also elucidate the protective effect of suloctidil against cerebral hypoxia.

Animals↗

PubMed1986

Inhibition of platelet thromboxane generation by suloctidil in man.

Oral administration of 100 or 200 mg suloctidil to healthy volunteers resulted in serum thromboxane B2 (TxB2) inhibition. This reached a maximum level between 90 min and 4 h after drug ingestion. TxB2 levels returned to 75% of basal values 6 h after 100 mg and more than 8 h after 200 mg, reaching control values at 24 h. Different experiments were performed to define the metabolic step at which suloctidil acts to inhibit serum TxB2 generation. Suloctidil prevented TxB2 synthesis also when platelet-rich plasma was stimulated by exogenous arachidonic acid or whole blood was clotted in the presence of exogenous arachidonic acid. This rules out the possibility that it inhibits phospholipases. No rediversion of prostaglandin synthesis after suloctidil occurred concomitantly with TxB2 inhibition, suggesting that the drug is not a selective thromboxane synthase inhibitor. In contrast, a significant reduction of serum PGE2 formation was found, suggesting a mechanism of action of suloctidil involving inhibition of cyclo-oxygenase. This was supported by the finding that PGI2 production by rat smooth muscle cells stimulated with arachidonic acid was significantly prevented by suloctidil in vitro. Suloctidil, however, did not prevent aspirin-induced inhibition of serum TxB2 generation. Blockade of platelet cyclo-oxygenase activity by suloctidil is therefore exerted at a level different from that of aspirin. In conclusion, suloctidil is a relatively weak nonselective cyclo-oxygenase inhibitor whose effect on platelet TxA2 production hardly accounts for its reported inhibitory effect on platelet aggregation.

Adult↗

PubMed1983

[Effect of suloctidil on the contractions of isolated rat aortic strips induced by norepinephrine and CaCl2].

The mode for the antispasmodic action of suloctidil was examined using aorta strips of rats in vitro. Both 10 microM suloctidil and 0.1 microM verapamil non-competitively inhibited the norepinephrine (NE)-induced contraction, of which pD'2 values were 4.61 +/- 0.41 and 6.16 +/- 0.22, respectively. Prazosin at 1 nM competitively inhibited the NE-induced contraction, and its pA2 value was 9.84 +/- 0.15. In the depolarized aorta, suloctidil competitively inhibited the CaCl2-induced contraction at the concentrations of 0.1 and 1.0 microM, of which the pA2 value was 5.96 +/- 0.26. However, 10 microM suloctidil inhibited the CaCl2-induced contraction in a non-competitive manner, and its pD'2 value was 5.01 +/- 0.14. The pA2 values for papaverine, verapamil and cinnarizine were found to be 5.23 +/- 0.10, 7.53 +/- 0.09 and 7.11 +/- 0.11 in CaCl2 induced contraction, respectively. In a Ca2+ free medium, 1 microM NE caused a transient contraction, which was maximum (23.8 +/- 2.2% of that in a normal solution) at 0.4 min after the application of NE. Subsequent application of 2.5 and 10 mM CaCl2 evoked a gradual contractile response, of which the maximum was 103.1 +/- 4.2% and 133.8 +/- 10.3% of that in a normal solution, respectively. Initial phasic contraction induced by NE in a Ca2+ free medium was not affected by 10 microM suloctidil nor by 0.1 microM verapamil, while this contraction was significantly suppressed by 1 nM prazosin. The tonic contraction, however, induced by re-application of CaCl2 was significantly suppressed by 10 microM suloctidil, 0.1 microM verapamil and 1 nM prazosin. Furthermore, 1.0 microM suloctidil and 0.1 microM verapamil significantly suppressed the 45Ca uptake into the depolarized aorta 5 and 10 min after the addition of 45CaCl2. On the contrary, suloctidil had no influence on the phosphodiesterase activity prepared from the aorta of rats even at 10 microM, whereas 1.0 microM papaverine inhibited the enzyme activity. It is concluded that suloctidil and verapamil inhibit the contractions of the isolated rat aorta induced by NE and CaCl2 through the inhibition of the influx of Ca2+ without affecting the intracellular Ca2+ release.

Animals↗

PubMedDate not supplied

A secondary prevention, randomized trial of suloctidil in patients with a recent history of thromboembolic stroke.

Four hundred and thirty-eight patients who had suffered a thromboembolic stroke not less than two weeks or more than four months previously, were entered into a placebo-controlled randomized clinical trial to determine whether suloctidil (200 mg t.i.d.) would influence the subsequent recurrence of stroke, the occurrence of myocardial infarction, or cardiovascular death. The two treatment groups were comparable at baseline with respect to important prognostic variables and there was good adherence to the study protocol during an average follow-up of 20 months. Significantly more patients complained of side-effects in the suloctidil group and more hepatotoxicity was also reported in the suloctidil group. Four cases of clinical hepatitis were suspected to be due to suloctidil, each of which was reversible on termination of study treatment; relative increases in SGOT and SGPT at three months in the suloctidil group were found to be mild and transient. The primary analysis of efficacy was based on the incidence of the first event of stroke, myocardial infarction or cardiovascular death, but excluding events that occurred more than 28 days after complete withdrawal from study medication for whatever reason. Thus, the primary analysis included 38 events in the suloctidil group and 47 in the placebo group (p = 0.17) representing a risk reduction of 24%. If total mortality is substituted for cardiovascular death, the corresponding figures are 47 in the suloctidil group and 58 in the placebo group (p = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrovascular Disorders↗

PubMed1983

[Effect of suloctidil on the dynamics of the peripheral artery of the dog].

The effects of suloctidil, an antispasmodic agent, on the femoral, renal, superior mesenteric, common carotid and vertebral blood flows were compared with those of papaverine and cinnarizine using electromagnetic flow meters in pentobarbital anesthetized dogs. In i.v. administration, the peripheral vasodilating action of suloctidil, papaverine and cinnarizine dose-dependently occurred from the dose of 0.1 mg/kg, and the order of their potencies in blood flow increase was vertebral greater than or equal to femoral greater than or equal to common carotid much greater than mesenteric artery. However, the renal blood flow decreased by i.v. administration of suloctidil and papaverine. I.a. administration (1-100 micrograms/kg) of suloctidil, papaverine and cinnarizine dose-dependently increased femoral and common carotid blood flows. I.a. administered suloctidil and papaverine caused a transient increase of renal blood flow followed by a slight decrease. Suloctidil-induced increase of femoral blood flow was not affected by the pre-treatment with atropine, propranolol or diphenhydramine. Thus, suloctidil may cause direct vasodilation to increase regional blood flow, and its influence on the various blood flows is roughly similar to those of papaverine and cinnarizine.

Animals↗

PubMed1985

An evaluation of suloctidil in the prevention of deep vein thrombosis in neurosurgical patients.

Suloctidil (200 mg t.i.d.) was compared with placebo in a randomized, double-blind trial to assess its value in preventing deep venous thrombosis (DVT) in high-risk neurosurgical patients, comprising 136 patients with brain or spinal tumour, head or spinal injury, or subarachnoid or intracranial hemorrhage. 125I fibrinogen leg scanning and impedance plethysmography were performed for up to 14 days to detect DVT. The two groups were also evenly balanced for DVT risk factors. Seventeen of 68 patients (25%) (95% confidence interval, 15-35%) treated with suloctidil and 12 of 68 patients (21%) (95% confidence interval, 11-32%) treated with placebo developed deep venous thrombosis. This observed difference in outcomes is not statistically significant (X2 = 1.096; p = 0.30). The estimated 95% confidence interval for the true difference in the incidence of DVT between suloctidil-treated and placebo-treated patients ranges from an 11% benefit in favour of suloctidil to an 18% benefit in favour of placebo. Major deep vein thrombosis occurred in two patients on suloctidil and three patients in the placebo group; there were no fatal pulmonary emboli during the 14-day study period, during which time four patients in each group died of non-thromboembolic complications. There was no observed difference in hemorrhagic complications. Long-term outcomes at three-months follow-up were similar between the two treatment groups. It is concluded that there is no real evidence that suloctidil (200 mg t.i.d.) is an effective regimen for the prevention of DVT in high-risk neurosurgical patients.

Brain Neoplasms↗

PubMed1979

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.

Animals↗

PubMed1984

Inhibition by suloctidil of [3H] nitrendipine binding to cerebral cortex membranes.

[3H] Nitrendipine binds specifically with high affinity and high capacity (KA congruent to 0.20 +/- 0.01 nM, Bmax = 4.4 +/- 0.3 pM/g tissue, means +/- S.E.M.; N = 4) to guinea-pig cerebral cortex membranes. Suloctidil fully inhibits [3H] nitrendipine binding with a Ki value of 0.45 microM. The interaction between suloctidil and the putative Ca2+ channels is allosteric as shown by competition experiments performed in the presence of D 600 or diltiazem. Comparison of the activity of some close analogs of suloctidil provides evidence for the importance of the amino group and of the hydrophobic amino substituent in the interaction of suloctidil and the putative Ca2+ channel. It is suggested that part of the previously reported blockade of Ca2+ entry induced by suloctidil is due to a blockade of the Ca2+ channels.

Animals↗

PubMed1987

Stimulation of prostacyclin production in blood vessels by the antithrombotic drug suloctidil.

Suloctidil is a calcium antagonist with vascular relaxing activity and an antithrombotic agent: its antiplatelet action has been demonstrated in vivo, but is difficult to reproduce in vitro and the mechanism of this effect remains unknown. We have observed that suloctidil (10 microM) stimulated the release of prostacyclin (PGI2) from the rabbit aorta, the dog vena cava and the dog portal vein, in vitro. This effect could be explained by an increased mobilization of free arachidonic acid. Neither the inactive congener CP894S, nor the two calcium channel antagonists, verapamil and flunarizine, reproduced the stimulatory effect of suloctidil. Suloctidil acted selectively on the vascular endothelium: it stimulated the release of PGI2 from bovine aortic and human umbilical vein endothelial cells, but neither from the de-endothelialized rabbit aorta nor from the bovine aortic media. The stimulatory effect of suloctidil on the release of the platelet inhibitor PGI2 from the vascular endothelium might contribute to the known antiplatelet and antithrombotic activity of this drug.

Animals↗

PubMed1993

1H-NMR study of suloctidil-A23187 calcium ionophore interaction.

Suloctidil is a molecule with calcium antagonist properties, whose anti-ionophoretic effect has previously been reported. In the presence of A23187 calcium ionophore free acid (A+), the NMR spectra of suloctidil (S +/-) are modified at the level of H-1 protons and to a lesser degree in the CH3-3 and aromatic regions. Experiments with one of the enantiomers of suloctidil and decoupling investigations led us to postulate the existence of diastereoisomers S+/A+, S-/A+ in the suloctidil +/-/A23187 + mixture. Moreover our results allow the hypothesis that suloctidil and calcium compete for the same binding site of the ionophore molecule.

Calcimycin↗

PubMed1983

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.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1984

Hypocholesterolaemic activity of suloctidil: double-blind, crossover short-term and long-term treatment trial.

Two studies were carried out in patients with primary hyperlipidaemia to investigate the effect of suloctidil (200 mg 3-times daily) on serum cholesterol levels and other lipidaemic variables. The first study was a double-blind, crossover comparison of suloctidil and placebo in 23 patients. Patients were allocated at random to receive one or other treatment for 4 weeks, after a wash-out period of 4 weeks on placebo, and were then crossed over to the alternative medication for the following 4 weeks. Patients were kept on a controlled diet throughout the trial. In the second, long-term study, 28 patients were treated, after an initial washout period of 8 weeks on placebo, with suloctidil for periods of up to 1 year. As in the short-term trial, patients were maintained on a controlled diet. The results showed that suloctidil produced a statistically significant reduction in total serum cholesterol and serum triglycerides in the short-term and this reduction was maintained over the longer period of the second study. In addition, there was a concomitant and approximately proportional increase in HDL-cholesterol. Suloctidil was well tolerated and no serious side-effects were reported.

Body Weight↗

PubMed1985

Suloctidil treatment prevents the development of post-traumatic feline spinal cord ischemia.

The effects of suloctidil (1.0 mg/kg i.v.) on white matter spinal cord blood flow (SCBF) and somatosensory evoked potential (SEP) conduction were assessed in a feline lumbar spinal cord contusion model. SEP conduction ceased immediately after a 500 g-cm injury and did not recover. SCBF following suloctidil declined by only 12% from pre-injury levels over the 4 hr experiment as compared to a 42% decline observed following vehicle injection. Accordingly, 7/8 vehicle cats, but only 1/5 suloctidil-treated cats, had 4 hr SCBF values of less than 10 ml/100 g/min. Bradycardiac and hypotensive effects of suloctidil were also noted. The ability of suloctidil to prevent post-traumatic ischemia may be useful in the acute treatment of spinal cord injury.

Animals↗

PubMed1982

A double-blind trial of suloctidil v. placebo in intermittent claudication.

In a recent double-blind trial lasting over 6 months, 40 patients suffering from intermittent claudication were randomly allocated to receive 300 mg of suloctidil per day or exactly matching placebo capsules. In addition to treadmill walking distance, other objective criteria including ankle blood pressure response and muscle blood flow measured by 133Xe clearance were used to assess the effectiveness of therapy. Nine patients (4 in the suloctidil group and 5 controls) did not complete the trial according to the protocol. Of the remaining 31 patients, 17 were in the control group and 14 received suloctidil. A significant improvement in the absolute walking distance, the level of beta-thromboglobulin (beta TG) compared to pre-therapy value and the time for the ankle pressure index to return to the pre-exercise value was observed in patients receiving suloctidil.

Adult↗

PubMed1986

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.

Animals↗

PubMed1986

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.

Adult↗