Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Molsidomine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1992

[Evaluation of the effects of molsidomine and propranolol-molsidomine combination on portal hemodynamics by pulsed Doppler ultrasound].

Molsidomine, a long acting vasodilator with antianginal properties, has been shown to decrease porto-hepatic pressure gradient in patients with cirrhosis. The present study aimed at assessing the effects of molsidomine, propranolol and of the association of these two drugs on portal vein blood flow as measured using Doppler and B-mode sonography. In 10 patients without liver disease (group 1), portal flow time average mean velocity (TAV) and portal vein blood flow (PVBF) were measured under basal conditions, 1 hour then 2 hours after ingestion of 4 mg of molsidomine. The same measurements were performed in 15 patients with cirrhosis (group 2) under basal conditions, 1 then 2 hours after double-blind administration of either molsidomine (10 patients) or placebo (5 patients). Fifteen further patients with cirrhosis (group 3) were studied after the double blind administration of 80 mg of propranolol and two hours later of 4 mg of molsidomine (10 patients) or placebo (5 patients); TAV and PVBF were measured under basal conditions, two hours after propranolol ingestion or placebo, then one and two hours after molsidomine or placebo ingestion. TAV and PVBF remained unchanged in patients treated with placebo. Molsidomine reduced TAV by 23.8 +/- 19.5% in group 1 (P < 0.01) and by 25.6 +/- 21.4% in group 2 (P < 0.01). In group 3, a 10% decrease was observed after propranolol (NS). When molsidomine was added, TAV was further decreased (-17.6 +/- 13.3% vs baseline, P < 0.01). PVBF remained unchanged in the three groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Short- and long-term effects of molsidomine retard and molsidomine nonretard on exercise capacity and clinical status in patients with stable angina: a multicenter randomized double-blind crossover placebo-controlled trial.

A multicenter, randomized, double-blind, crossover, placebo-controlled study was conducted in 90 isosorbide dinitrate responders showing stable angina to compare the efficacy of molsidomine retard, 8 mg b.i.d., with that of molsidomine, 4 mg t.i.d., for 6 weeks. Total work performance (workload x min) was significantly improved, compared with baseline and placebo until 8 and 12 h after molsidomine and molsidomine retard administration, respectively. ST-segment depression decreased significantly under the two treatments at 60 W as well as at maximal exercise. The rate-pressure product (heart rate x systolic blood pressure) decreased and increased significantly at submaximal and maximal exercise level, respectively. All these effects remained significant after 6-week treatment, with only the ST segment showing a nonsignificant tendency to improvement at maximal work. The frequency of anginal attacks and of sublingual nitroderivative-tablets consumption decreased significantly with molsidomine, 4 mg, and molsidomine retard, 8 mg. However, overall results showed that the latter form reduces myocardial ischemia more efficiently at submaximal exercise level, has a more prolonged effect on exercise tolerance, and maintains it at a somewhat higher level after 6-week treatment.

Adult↗
PubMed1994

The ESPRIM trial: short-term treatment of acute myocardial infarction with molsidomine. European Study of Prevention of Infarct with Molsidomine (ESPRIM) Group.

Previous small clinical trials have suggested that treatment with nitric oxide donors in suspected myocardial infarction can reduce mortality by 30-35%. To confirm this finding in a large-scale trial, we compared molsidomine and its active metabolite linsidomine (a nitric oxide donor) with placebo in 4017 patients with acute myocardial infarction. In our trial, patients without signs of overt heart failure (Killip III/IV) were randomly assigned in a double-blind design within 24 h of symptom onset to receive linsidomine 1 mg/h intravenously for 48 h, followed by 16 mg molsidomine by mouth daily for 12 days (n = 2007), or an identical placebo (n = 2010). All other treatments could be used at the responsible physician's discretion with the exception of systematic vasodilator treatment. The molsidomine and placebo groups showed similar all-cause 35-day mortality (168 [8.4%] vs 176 [8.8%] deaths, p = 0.66), and adjustment for baseline variables in a Cox model had no effect. Similarly, we found no difference for long-term mortality (mean follow-up 13 months; 294 [14.7%] vs 285 [14.2%] deaths, p = 0.67). The two groups showed similar frequencies of major and minor adverse events; only headache was significantly more common in the molsidomine group. Changes in treatment practices and the lower risk profile of our study subjects than of participants in previous trials may explain the results. It is still not clear whether nitric oxide donors can improve survival in higher-risk myocardial infarction patients.

Administration, Oral↗
PubMed2003

A pilot double-blind randomized placebo-controlled study of molsidomine 16 mg once-a-day in patients suffering from stable angina pectoris: correlation between efficacy and over time plasma concentrations.

OBJECTIVES: A new once-a-day (o.a.d.) formulation of molsidomine (16 mg) was evaluated in patients with stable angina pectoris. The aims were to characterize its pharmacokinetics after a single dose, to demonstrate its clinical efficacy and safety versus placebo and to investigate correlations between pharmacokinetics and pharmacodynamics. METHODS: Forty-two patients were recruited in a double-blind, crossover, randomized placebo-controlled trial. The pharmacokinetics of molsidomine and SIN-1, its active metabolite, were determined at specific time points (3, 6, 10, 14, 18, 22 and 24 h) after the administration of a single dose of molsidomine 16 mg o.a.d. in all patients distributed into seven groups. Twenty-eight of these 42 patients showed a positive baseline cycloergometric exercise test response during the run-in placebo period and were used to compare the efficacy of molsidomine to placebo. Relationships between plasma concentration in molsidomine or SIN-1 and ischemic threshold were assessed in 16 of the 28 patients with a positive exercise test at baseline. Indeed, the censored variable ischemia-limited tolerance to exercise could not be evaluated in those patients who did not show exercise-induced ischemia anymore under molsidomine 16 mg o.a.d. Pharmacokinetic-pharmacodynamic relationships were evaluated using regression models and correlation coefficients. RESULTS: The highest average concentration in molsidomine and SIN-1 occurred after 6 h, then a plateau of 15-20 ng/ml molsidomine and 0.8-3.0 ng/ml SIN-1 was maintained for at least 8 h and the mean residual molsidomine concentration 24 h post-drug intake was around 8 ng/ml, still in the effective range of 5-10 ng/ml. A significant increase in total workload (+52 W min, P=0.009), total exercise time (+32 s, P=0.003) and time to angina (+25 s, P=0.016) was measured with molsidomine 16 mg o.a.d. relative to placebo. Using linear regression, significant correlation coefficients were determined between molsidomine plasma concentrations (but not SIN-1) and exercise test improvements (r=0.827, P<0.001 for the total workload; r=0.772, P<0.001 for the total exercise time; and r=0.566, P=0.028 for the time to 1 mm ST-segment depression). CONCLUSION: The pharmacokinetics of molsidomine 16 mg in patients with stable angina pectoris is compatible with a o.a.d. dosage regimen. This o.a.d. formulation is effective and well-tolerated, providing a 24-h therapeutic control of myocardial ischemia. A positive and significant linear relationship between molsidomine plasma concentration and the increase in exercise tolerance was observed.

Aged↗
PubMed1981

[Ergometric study of a new vasodilator agent in angina: molsidomine. Value of combination with beta-blockaders].

Molsidomine, a new venous vasodilator, was studied in 40 cases of stable angina by ergometric stress testing. 1. In 10 patients, one hour after 2 mg molsidomine sublingually, the work inducing a 1 mm ST depression (WST 1) increased by 94% (p less than 0,05), the total work by 52% (p less than 0,005) and the maximum ST depression (ST max) fell by 45% (p less than 0,01). Resting heart rate was unchanged. There was a mild fall in systemic blood pressure. 2. Molsidomine had a significant synergic effect in 3 groups of 10 patients on betablocker therapy but with ischaemic changes on exercise: a) Molsidomine 1 mg sublingually increased WST 1 by 36% (p less than 0,05); at a 2 mg dosage, by 55% (p less than 0,001). ST max decreased from 2,4 +/- 0,4 mm to 1,3 +/- 0,3 (p less than 0,005) and 1,2 +/- 0,33 (p less than 0,001) respectively. The maximal effect was obtained with 1 mg in 5 out of 10 patients. b) One and three hours after 2 mg Molsidomine sublingually or orally: WST 1 increased from 97% to 110% (p less than 0,005): ST max decreased in similar proportions (p less than 0,005). c) 2 mg Molsidomine and 230 mg isosorbide dinitrate orally were compared after two hours: WST 1 increased by 130% after Molsidomine (p less than 0,005) and by 112% after isosorbide (p less than 0,005). ST max decreased in similar proportions (p less than 0,005). The blood pressure fell less with molsidomine. Molsidomine appeared to be better tolerated than isosorbide. (5 cases of mild headache in 40 patients compared to 4 cases out of 10 patients). The results of a preliminary clinical trial are reported. The association of molsidomine (2 mg per os three times daily) reduced the number of anginal attacks by over 50% in 16 out of 17 patients inadequately controlled by betablockade alone. 3 patients complained of headache at the onset of therapy. The efficacity was comparable and the tolerance better than in 28 patients with isosorbide dinitrate and betablockade, and in 10 patients with nifedipine and betablockade. In conclusion, molsidomine is a venous vasodilator with useful pharmacokinetic properties. It seems to be effective and well tolerated in the treatment of angina whether used alone or in association with betablockers.

Administration, Oral↗
PubMed1985

The activity of molsidomine in experimental models of ischemic cardiac disease.

The cardioprotective and antithrombotic activity of molsidomine, a novel therapeutic agent for the treatment of coronary heart disease, was investigated in a series of animal models of myocardial ischemia. Molsidomine given to dogs with marked ST segment elevation (epicardial electrogram), induced by a reduction of left descending coronary artery (LAD) flow to 20% to 30% of the original value, resulted within 40 minutes in complete normalization of ECG changes. In another animal model molsidomine given either before or after occlusion of the LAD significantly reduced infarct size. All these molsidomine effects were accompanied by a marked lowering of preload, resulting in a reduction of extravascular coronary artery resistance and in increased blood flow toward the ischemic zones. In a model of myocardial ischemia and reperfusion in the anesthetized dog, molsidomine had a marked protective effect against the incidence of spontaneous ventricular fibrillation. This effect could also be attributed to the anti-ischemic activity of molsidomine, which would reduce the disparity between the refractory periods in normal and ischemic areas and thus increase ventricular stability. The antithrombotic activity of molsidomine was investigated in dogs in which the left circumflex coronary artery was electrically stimulated, a procedure that leads to thrombotic occlusion. Molsidomine in a dose-dependent manner prevented coronary thrombotic occlusion and reduced thrombus wet weight and the size of the resulting infarction. These effects of molsidomine were not related to its hemodynamic activity, since nitroglycerin and isosorbide dinitrate had similar hemodynamic effects but did not prevent coronary thrombosis. The antithrombotic activity of molsidomine is probably related to its ability to lower coronary venous blood thromboxane levels.

Animals↗
PubMed1985

Relationship between pharmacokinetics and pharmacodynamics of molsidomine and its metabolites in humans.

The pharmacokinetic properties and hemodynamic effect of molsidomine and its pharmacologically active metabolite SIN-1 were investigated in 13 healthy volunteers following single oral doses. Hemodynamic changes were measured by finger plethysmography (peripheral arterial resistance), impedance plethysmography (venous distensibility), heart rate, and blood pressure. Plasma concentrations of molsidomine, SIN-1, and SIN-1C were measured by means of high-pressure liquid chromatography. Oral administration of rapidly dissolving tablets of molsidomine (2 tablets of 4 mg), a sustained-release form of molsidomine (8 mg), and SIN-1 (4 mg) caused an increase of the a/b ratio of the finger plethysmogram and an increase of the venous distensibility. Heart rate and blood pressure remained unaffected. The time course of the peripheral arterial effect mimicked the time course of plasma concentrations of molsidomine and SIN-1. Similar to the results in animals, molsidomine was metabolized in humans to SIN-1 and subsequently degraded to the inactive metabolite SIN-1C. The kinetic profile of both metabolites could be followed in the plasma. The rate-limiting step in the metabolic sequence of molsidomine was found to be enzymatic hydrolysis and decarboxylation of molsidomine to SIN-1. Concentration-response curves of the a/b ratio of the finger plethysmogram showed that the plasma concentrations required to produce a definite effect are much higher for molsidomine than for SIN-1. This shows that the pharmacodynamically active form of molsidomine in humans is the metabolite SIN-1. The changes in the finger plethysmogram produced by SIN-1 suggest that in addition to the effect on the venous site, SIN-1 also dilates the peripheral arterial site.

Adult↗
PubMed1996

Haemodynamic effects of combined treatment with molsidomine and propranolol on portal hypertension in conscious and unrestrained cirrhotic rats.

We investigated the systemic and splanchnic haemodynamic effects of combined treatment with molsidomine and propranolol on cirrhotic rats. Liver cirrhosis was produced by repeated intraperitoneal injections of thioacetamide. The blood flow of each organ was measured serially using the radioactive microsphere method in the awake state before and after the administration of each agent. Cirrhotic rats received molsidomine (0-.5 mg/kg), propranolol (0.1 or 0.2 mg/min), both agents or placebo. Combination treatment with molsidomine and 0.1 mg/min propranolol significantly reduced portal pressure compared with molsidomine or propranolol alone (21 +/- 4 vs 15 +/- 3 or 11 +/- 2% P < 0.05). Systemic haemodynamic changes with this combined treatment were mild. This combined treatment slightly inhibited the molsidomine-induced decrease in portal vascular resistance (27 +/- 9 vs 31 +/- 6; NS) and markedly inhibited the molsidomine-induced decrease in splanchnic arterial resistance (7 +/- 6 vs 27 +/- 5% P < 0.05). Compared with low-dose propranolol administration, the combined treatment was associated with a significant decrease in portal vascular resistance (27 +/- 9% decrease vs 2 +/- 2% increase; P < 0.001) and a significant decrease in splanchnic arterial resistance (7 +/- 6% decrease vs 5 +/- 4% increase P < 0.05). The combination of molsidomine and high-dose propranolol (0.2 mg/min) caused a marked reduction in portal venous inflow, mean arterial pressure and cardiac index. We conclude that propranolol enhances the molsidomine-induced decrease in portal pressure by splanchnic vasoconstriction in association with a slight decrease in portal vascular resistance. The combination therapy with molsidomine and low-dose propranolol combination had more beneficial and less harmful effects on systemic and splanchnic haemodynamics and thus appears to be a superior method for treating portal hypertension.

Animals↗
PubMed2003

No effect of highly dosed nitric oxide donor molsidomine on the angiographic restenosis rate after percutaneous coronary angioplasty: a randomized, placebo controlled, double-blind trial.

BACKGROUND: Nitric oxide (NO) counteracts several mechanisms involved in the restenotic process after coronary angioplasty. NO mediates an antiproliferative effect on smooth muscle cells, inhibition of leukocyte-vessel wall interactions, and platelet aggregation and adhesion. Because these effects are mainly dose dependent, NO-releasing drugs have to be applied at a high dose to have an effect on restenotic mechanisms. OBJECTIVES: To study the effect of the NO donor molsidomine at a high dose of 8 mg tid on angiographic restenosis rate in a randomized, placebo controlled, double-blind trial. PATIENTS AND METHODS: One hundred and sixty-six patients with de novo stenosis were randomly assigned to molsidomine or placebo treatment for six months (83 patients each). The primary end point was the angiographic restenosis rate at six months. The secondary end points were major adverse cardiac events (MACE) including death, myocardial infarction and revascularization. Analyses were performed by intention to treat. RESULTS: There were no differences in clinical, procedural and angiographic data, including minimum lumen diameter and reference diameter. Provisional stenting was performed in 28% of patients receiving molsidomine and 25% of patients treated with placebo. All other patients were treated with standard balloon angioplasty. Reangiography rate was 89.3% (molsidomine 90 lesions, placebo 97 lesions). Restenosis rate (greater than 50% diameter stenosis) was not significantly different (molsidomine 25.6% and placebo 29.9%). Patients receiving molsidomine improved significantly more in their anginal class than patients receiving placebo (P<0.026). Occurrence of MACE did not significantly differ between both groups (molsidomine 26.8% and placebo 34.9%, P=0.26). CONCLUSION: Treatment with the NO donor molsidomine at a high dose of 8 mg tid for six months after coronary angioplasty has no effect on the angiographic restenosis rate. Due to the vasodilating effect of NO, the anginal status improves slightly more in patients receiving molsidomine.

Administration, Oral↗
PubMed1993

[Molsidomine in chronic heart failure with liver congestion--oral or intravenous therapy?].

Patients suffering from congestive heart failure combined with gastrointestinal congestion often present irregular resorption and metabolism of orally applicated cardiovascular drugs. Intravenous therapy therefore is used very often for those patients. In this trial we compared the efficiency of molsidomine given either orally or intravenously in patients suffering from congestive heart failure. We investigated ten patients (54.6 +/- 13 years) with congestive heart failure (NYHA III and IV) and a central venous pressure > 10 mmHg. Five patients of group A were given 4 mg of molsidomine intravenously on the first day and an oral dose of 4 mg of molsidomine on the second day. The five patients of group B received the oral dose on the first day and intravenous treatment on the second day. Central venous pressure and plasma levels of molsidomine and of the effective metabolite SIN-1 were measured before as well as ten, 20, 40, 60 minutes, two, four and eight hours after application of molsidomine. Central venous pressure decreased significantly up to two hours after molsidomine in both oral and intravenous groups (p < or = 0.01). There was no relevant difference between the oral and the intravenous group. The hemodynamic parameters correlated with molsidomine plasma levels. According to our results the efficiency of oral molsidomine does not differ from intravenous molsidomine in patients with congestive heart failure.

Administration, Oral↗
PubMed2002

Molsidomine enhances the protective activity of valproate against pentylenetetrazole-induced seizures in mice.

Molsidomine (25 mg kg(-1)), a donor of nitric oxide, commonly used in the treatment of coronary artery disease, enhanced the protective activity of valproate against the clonic phase of pentylenetetrazole-induced seizures in mice, significantly reducing the ED(50) of valproate from 123.5 to 78 mg kg(-1). Molsidomine was found to be ineffective with respect to the protective action of clonazepam, ethosuximide and phenobarbital. Alone, molsidomine in a dose of 25 mg kg(-1) was ineffective in this model of seizures. Since N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthase, failed to reverse the effect of molsidomine on valproate, an involvement of nitric oxide in the mechanism of the anticonvulsive efficacy of valproate does not seem to be probable. Molsidomine (25 mg kg(-1)) significantly elevated the free plasma level of valproate from 33.8 to 46.2 microg ml(-1). Therefore, we conclude that the interaction of molsidomine with valproate is at the pharmacokinetic level. The combination of valproate with molsidomine appears beneficial because is free from adverse effects, in terms of motor impairment and long-term memory deficit. Our results suggest that the dosage of valproate in patients with coronary artery disease treated with molsidomine should be decreased. It would allow us to reduce adverse effects of valproate.

Animals↗
PubMed1985

Pharmacokinetics of molsidomine in humans.

The pharmacokinetics of molsidomine were investigated in the plasma and urine of healthy male volunteers and patients with coronary heart disease after intravenous and/or oral administration of different galenic dosage forms of molsidomine. Following the rapid attainment of mean peak concentration (15 +/- 7 mg/ml) 0.5 to 1.0 hour after single oral dosing of 2 mg of molsidomine, the plasma levels of the unchanged drug decline monoexponentially with a mean half-life of 1.6 +/- 0.8 hours. Molsidomine is absorbed almost completely. Its absolute bioavailability (44 +/- 15%) and a 14C-labeled triale give evidence of quick biotransformation of molsidomine to active metabolites. Less than 2% of the unchanged drug appear in the urine, but renal excretion is the main route of elimination of the metabolites in humans (90% to 95%). The kinetics parameters after administration of multiple dosages of 4 mg of molsidomine over 29 days do not account for accumulation of or enzyme induction by molsidomine. The finding of obvious good correlations between plasma levels of the predrug molsidomine and corresponding pharmacodynamic data can be made plausible by the time course of concentration values of the active metabolite SIN-1 in plasma.

Animals↗
PubMed2003

The nitric oxide donor molsidomine improves survival and reduces hepatocyte apoptosis in cholestasis and endotoxemia.

BACKGROUND: Cholestasis and endotoxemia have been demonstrated to cause hepatocyte apoptosis through caspase-mediated pathways. In vitro nitric oxide (NO) donors reduce hepatocyte apoptosis and caspase activation in several models. The nitric oxide donor molsidomine improves survival in an in vivo model of endotoxemia. We tested the effect of molsidomine on survival and hepatocyte apoptosis in a model of obstructive jaundice and endotoxemia. STUDY DESIGN: Sprague-Dawley rats underwent common bile duct ligation on day 1. On day 3, animals were given either 100 mg/kg of molsidomine or an equivalent volume of saline, and 30 minutes later they were given endotoxin 3 mg/kg or 10 mg/kg intravenously. Animals were sacrificed 4 or 16 hours after endotoxin injection. Serum samples were analyzed for alanine aminotransferase and frozen liver samples were analyzed for caspase 3 activity. Paraffin-embedded liver sections were assayed for apoptosis using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Survival was measured in a separate experiment in which animals underwent the same protocol, but were given three different doses of endotoxin and were observed for 72 hours before sacrifice. RESULTS: At endotoxin 3 mg/kg, the 72-hour survival in saline-treated animals was 92%, which decreased to 45% at 10 mg/kg and to 29% at 15 mg/kg. All of the molsidomine-treated animals survived all endotoxin doses. Alanine aminotransferase was reduced in molsidomine-treated animals compared with those treated with saline. Apoptosis was attenuated in molsidomine-treated animals. Caspase 3 activity was decreased in molsidomine-treated animals compared with those given saline. CONCLUSIONS: Molsidomine attenuates caspase activation and hepatocyte apoptosis and improves survival after cholestatic endotoxic injury.

Animals↗
PubMed1987

Acute and chronic effects of molsidomine on pulmonary artery pressure and work capacity in patients with coronary heart disease.

To test the clinically supposed development of tolerance during chronic molsidomine therapy we studied a total of 11 patients with angiographically-proven coronary heart disease at rest and during ergometric exercise (supine position; submaximal, i.e. 50 W for 3 min, and maximal exercise). Pulmonary arterial pressure (PAPmean, floating catheter), arterial blood pressure (RR, cuff method), work capacity (W x min) and duration of exercise loading (sec) were measured at rest and on exercise before and during chronic (4 weeks) oral therapy with 3 x 4 mg day-1 of molsidomine. Acute administration of 4 mg molsidomine reduced the mean arterial resting pressure by 12% and under submaximal exercise loading by 8%. After molsidomine, the PAPmean was reduced by 35% at rest; following a period of treatment of 4 weeks no significant decrease in efficacy could be discerned (PAPmean reduction by 31%). Under submaximal and maximal exercise the PAPmean dropped by 44% and 37%, respectively (35.5 +/- 6.7 cf. 19.9 +/- 4.5 mmHg; 39.2 +/- 6.5 cf. 24.8 +/- 7.0 mmHg), whilst simultaneously the work capacity increased by 93% (281 +/- 108 cf. 545 +/- 254 W x min). After 4 weeks treatment with 12 mg day-1 of molsidomine, the PAPmean of 22.4 +/- 6.6 mmHg and 30.1 +/- 9.9 mmHg under identical exercise loading conditions, remained significantly below the exercise load value prior to the onset of medication. The molsidomine-induced increase in the exercise tolerance was maintained throughout the long-term medication (537 +/- 268 W x min). With a four-week treatment with daily doses of molsidomine there was a persistent effect on the pulmonary arterial pressure and the work capacity. Thus development of tolerance during high dose, long-term molsidomine therapy is not to be expected.

Adult↗
PubMed2000

Protective effect of the nitric oxide donor molsidomine on indomethacin and aspirin-induced gastric injury in rats.

OBJECTIVE: To study the effect of the nitric oxide donor, molsidomine, on gastric and duodenal injury induced by indomethacin and aspirin. METHODS: Sprague-Dawley rats weighing 180-200 g were used after 24 h fasting. Indomethacin (5 mg/kg) was given subcutaneously as a single dose and followed by multiple injections of histamine. Molsidomine (0.05 mg/kg) or distilled water was given by gavage 30 min before indomethacin and repeated at 3 h intervals for two doses. Rats were killed 2 h after the last dose of molsidomine. Aspirin (500 mg/kg) was given by gavage and repeated 2.5 h later. Molsidomine or distilled water was given 30 min before the initial aspirin dose and repeated after 2 h. Animals were killed 2.5 h after the second dose of aspirin. The severity of the gastric mucosal damage was graded from 0 to 3, and the duodenal bulb ulcer surface area calculated by two independent observers using a dissecting microscope. RESULTS: Indomethacin and aspirin resulted in significant gastric mucosal damage with median scores of 2 (interquartile ranges 1.4-3, n = 16 and 2-3, n = 10, respectively). Molsidomine significantly ameliorated indomethacin- and aspirin-induced damage with median scores of 1 (interquartile ranges 0.5-1.5, n = 19 and 0.6-1.9, n = 10, respectively; P<0.008 and P<0.02, respectively (Mann-Whitney Utest)). Molsidomine had no effect on duodenal bulb ulcerations caused by indomethacin. CONCLUSION: Oral molsidomine has a protective effect on gastric mucosa against damage induced by ulcerogenic agents. This could have an important clinical benefit, especially in cardiac patients taking aspirin in addition to a nitric oxide donor such as molsidomine.

Administration, Oral↗
PubMed1999

Inotropic effects of endothelin-1: interaction with molsidomine and with BQ 610.

-In vivo studies could not detect a positive inotropy of endothelin (ET)-1 as described in in vitro experiments. ET-induced direct positive inotropy, which seems to be mediated by ETB receptors, may be antagonized in vivo by an indirect cardiodepressive effect owing to an ET-induced coronary vasoconstriction via ETA receptors. This study compares the effects of a dose of 1 nmol/kg ET-1 alone on myocardial contractility and myocardial energy metabolism with the effects of 1 nmol/kg ET-1 after pretreatment with 5 mg/kg molsidomine or with 100 microg/kg of the ETA receptor antagonist BQ 610. We investigated the effects of ET-1 versus saline controls in open-chest rats. In addition to measurements in the intact circulation, myocardial function was examined by isovolumic registrations independent of peripheral vascular effects. We also studied the effect of ET-1 on myocardial high-energy phosphates. Pretreatment with molsidomine and BQ 610 attenuated the ET-induced reduction of cardiac output (ET-1: -62%; molsidomine+ET-1: -47%; BQ 610+ET-1: -27% different from controls). After a transient initial vasodilation, ET-1 raised total peripheral resistance (ET-1: +190%; molsidomine+ET-1: +171%; BQ 610+ET-1: +89%). BQ 610 was more effective in preventing ET-induced vasoconstriction. The increase of isovolumic peak first derivative of left ventricular pressure (ET-1: -2%; molsidomine+ET-1: +16%; BQ 610+ET-1: +19%) after pretreatment with molsidomine or BQ 610 indicates that these drugs unmask the positive inotropy of ET-1. ET-induced myocardial ischemia was abolished by molsidomine and BQ 610. Pretreatment with molsidomine or blockade of ETA receptors by BQ 610 can unmask the positive inotropy of ET-1 by preventing ET-induced myocardial ischemia. The positive inotropic effect of ET-1 seems to be mediated by ETB receptors.

Animals↗