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At least 19 recordsLinked to original sources
PubMed1979

Vasodilators in senile dementias: a review of the literature.

The rationale for the use of vasodilators in the aged has changed from the attempt to increase cerebral blood flow to the attempt to improve cerebral metabolism. Review of 102 studies of eight vasodilators showed that significantly more controlled studies claimed practical clinical benefit from drugs supposed to improve neuronal intermediary metabolism with secondary vasodilatation than from drugs supposed to have only vasodilator action (P less than .005). Studies of both classes of drugs often suffered from poor study design, inappropriate and inconsistent application of outcome measurements, as well as negative bias due to selection of severely demented subjects. Future studies should be placebo-controlled investigations of drugs with primarily metabolic action, address questions of dose and time response, consistently use appropriate outcome measurement, and concentrate on the elderly in whom cognitive improvement is possible.

Aged↗
PubMed1992

Serotonin-induced contractility in human saphenous vein is inhibited by naftidrofuryl.

Vascular endothelial denudation contributes to vasospasm by causing platelet aggregation and the subsequent release of vasoconstrictors such as serotonin. It has recently been suggested that naftidrofuryl fumarate (NFT) may oppose serotonin-induced vasoconstriction. Fourteen rings of human saphenous vein from 14 patients undergoing varicose vein surgery were tested in standard organ bath experiments. Cumulative dose-response curves and maximal contraction in response to serotonin were recorded and this was repeated in the presence of NFT at 10(-6) and 10(-3) mol/l. The difference in maximal contractility between the three sets of curves was significant (P < 0.0001). Sensitivity to serotonin in each of the three curves was measured using the concentration for half-maximal response; differences were again significant (P < 0.0001). It is concluded that NFT reduces serotonin-induced contractility in a dose-dependent fashion in rings of human saphenous vein in vitro. These results suggest a possible role for NFT in reducing vasospasm and support further investigation of this drug.

Dose-Response Relationship, Drug↗
PubMed1991

Naftidrofuryl protects the rat against chronic gastric ulceration.

Intraperitoneal reserpine (5 mg/kg every day for 5 days) produced solitary chronic ulceration of the rat stomach after 2 weeks. Gavage with 1 mL/day of 1% naftidrofuryl oxalate for 2 weeks protected 30% of rats against ulceration and this protection extended to 70% of cases with a 2% solution. Similar gavage with a 5% solution protected all rats against ulceration without significantly influencing the basal H+ output (14.8 +/- 0.6 versus 15.4 +/- 0.5 mumol, mean +/- SEM, n = 10); that is, cytoprotection was achieved.

Animals↗
PubMed1992

Postischemic breakdown in hippocampal protein synthesis and mnesic deficits in rats: pharmacological improvement by curative naftidrofuryl treatment.

This work was designed to investigate the effects of brain ischemia on mnesic retention in the model of unilateral microsphere embolization in rats. Using various radioactive tracers as well as a learning/memory test, we could correlate following parameters: regional blood flow, protein synthesis and memory retention. All were severely impaired by the hemispheric multi-infarction. A curative treatment with naftidrofuryl (15 mg/kg i.p.) for 3 consecutive days strongly improved the mnesic capacities of the animals, and this effect was corroborated by a marked protective drug action on protein synthesis in the hippocampus. Indeed, studies on valine incorporation into proteins revealed that, despite having no quantitative effect on regional blood flow, naftidrofuryl allowed an almost normal functioning of protein synthesis. As naftidrofuryl had also no direct effect on protein synthesis in the intact contralateral hemisphere, this effect was consequently attributed to the metabolic and/or antiserotoninergic effects of the drug.

Animals↗
PubMed1986

Conservative drug therapy and walking exercise in stage IIb peripheral arterial occlusion disease.

In cases of peripheral arterial occlusion disease in Fontaine's stage IIb (PAOD IIb) with a walking distance of less than 200 m, the therapy that has priority, besides removing risk factors, is physical exercise. Very often it seems that concomitant rheological treatment with drugs is advisable to support the therapy and to improve compliance. The experience gained in the last 30 months in the treatment of PAOD IIb in a large angiological outpatient establishment is presented. All the patients were given thorough medical examination before the start of the therapy, and their angiological and rheological status was recorded. Depending on the results of the examinations, the patients with PAOD IIb were given one of three treatment variants: Patients with a haematocrit less than 43% and moderately altered rheology (group I; therapy: physical exercise). Patients with a haematocrit less than 43% and severely altered rheology, in particular increased erythrocyte rigidity (group II; therapy: physical exercise combined with naftidrofuryl treatment). Patients with a haematocrit of 43% or more and severely altered rheology (group III; therapy: physical exercise with haemodilution combined with naftidrofuryl treatment). Before the drug treatment was started, the possibility of surgical reconstruction of the vessels or angioplasty was discussed and the conservative therapy was undertaken only after surgery or when surgery had been rejected. Every course of treatment included reducing the risk factors as far as possible. All three conservative therapies were implemented for a period of at least 6 months. The increase in the walking distance was 157% (n = 27) after physical exercise alone, 238% (n = 27) with the naftidrofuryl combination therapy and 311% (n = 27) with the naftidrofuryl/haemodilution combination therapy.

Adult↗
PubMed1991

A randomised controlled study to evaluate the effect of Naftidrofuryl in a rat ischaemic skin flap model.

The theoretical benefit of Naftidrofuryl in improving survival of ischaemic skin flaps was tested in a randomised controlled study using oral, intraperitoneal and local administration of the drug in three groups of Wistar rats. The vasodilator Naftidrofuryl was shown to be of no value in preventing distal necrosis in a rat skin flap model which has previously responded to pharmacological manipulation.

Animals↗
PubMedDate not supplied

A comparative study on the effect of various pharmacological agents on the survival of skin flaps in the rat.

The effects of chlorpromazine, pentoxifylline, terbutaline, allopurinol, phenoxybenzamine, naftidrofuryl, hydralazine and trimetazidine were investigated on caudally based dorsal flaps. The study was performed on 108 rats, divided in 9 groups of 12 animals each, one of which served as a control group. All treated groups showed a significantly greater survival of the flap than the control group. Comparisons among different groups showed better outcome in those receiving trimetazidine and hydralazine, followed by those receiving naftidrofuryl and phenoxybenzamine.

Allopurinol↗
PubMed1991

Involvement of serotonergic neuronal systems in the anti-amnesic action of naftidrofuryl oxalate.

The effects of naftidrofuryl oxalate on cycloheximide- and 5-hydroxytryptophan (5-HTP)-induced amnesia were investigated using a passive avoidance task in mice. Naftidrofuryl oxalate significantly improved the cycloheximide-induced amnesia. This effect of naftidrofuryl oxalate was antagonized by 5-HTP, a serotonin (5-HT) precursor, and by p-chloroamphetamine (PCA), a 5-HT releaser. Single administration of 5-HTP in combination with pargyline, a monoamine oxidase inhibitor, induced amnesia (5-HTP-induced amnesia). This amnesia was attenuated by ritanserin, a 5-HT2-selective antagonist, but not by pindolol, a 5-HT1-selective antagonist. Naftidrofuryl oxalate also attenuated the 5-HTP-induced amnesia. A binding study revealed that naftidrofuryl oxalate inhibited the binding of [3H]ketanserin to 5-HT2 receptors in mouse brain synaptic membrane in a dose-dependent fashion (IC50 = 1.42 x 10(-7) M), but did not inhibit that of [3H]serotonin to 5-HT1 receptors. These results suggest that naftidrofuryl oxalate may attenuate cycloheximide- and 5-HTP-induced amnesia by blocking 5-HT2 receptor subtypes.

Amnesia↗
PubMed1992

Effect of naftidrofuryl oxalate on 5-HT2 receptors in mouse brain: evaluation based on quantitative autoradiography and head-twitch response.

The effects of naftidrofuryl oxalate (LS-121) on 5-HT2 receptors in the brain were assessed in mice on the basis of quantitative autoradiography and head-twitch responses. LS-121 inhibited [3H]ketanserin (2 nM) binding in all brain areas assayed in which there were 5-HT2 receptors, such as the frontal cortex, cingulate cortex, parietal cortex, occipital cortex, temporal cortex, nucleus accumbens, caudate-putamen, olfactory tubercle and hippocampus. In the frontal cortex, which has the highest density of 5-HT2 receptors, the Ki value of LS-121 was 6.08 x 10(-8) M. The inhibitory potencies of methysergide and ritanserin for 5-HT2 receptors were about 16- and 60-fold stronger, respectively, than that of LS-121. Moreover, in behavioral studies, LS-121 (12.5-50 mg/kg i.p.) produced dose-dependent and significant inhibitory effects on head twitches induced by 5-hydroxytryptophan (5-HTP) plus pargyline, which is a 5-HT2 receptor-dependent behavior in mice. These results suggest that LS-121 inhibits 5-HTP plus pargyline-induced head twitches by blocking 5-HT2 receptors.

5-Hydroxytryptophan↗
PubMed1991

Naftidrofuryl oxalate, nootropic effects on the scopolamine- and the basal forebrain lesion-induced amnesia in rats.

We studied the effects of naftidrofuryl oxalate on scopolamine- and basal forebrain (BF) lesion-induced amnesia using passive avoidance and multiple T-maze tasks, in comparison with Ca-hopantenate and physostigmine in rats. In the passive avoidance task, one-week treatment with naftidrofuryl oxalate (12.5 and 25 mg/kg, IP) ameliorated BF lesion-induced amnesia. The multiple T-maze task was done with two training sessions per day for five continuous days. We measured the number of errors made from start box to goal box. Naftidrofuryl oxalate (12.5 mg/kg, IP, b.i.d.) and physostigmine (0.1 mg/kg, IP, b.i.d.) attenuated scopolamine- and BF lesion-induced amnesia. However, treatment with naftidrofuryl oxalate for one week failed to inhibit the decrease of the choline acetyltransferase induced by the BF lesion. Ca-hopantenate did not show attenuation of amnesia induced by the scopolamine or BF lesion. These results suggest that naftidrofuryl oxalate enhances the storage of spatial information, and that the nootropic effects of naftidrofuryl oxalate may be produced by an indirect activation of the cholinergic system through serotonergic neuronal systems.

Amnesia↗
PubMed1991

Effects of hypoxia and pharmacological treatment on enzyme activities in skeletal muscle of rats of different ages.

The activities of enzymes related to energy metabolism in the gastrocnemius and soleus muscles in young-adult (4 months), mature (12 months), and senescent (24 months) rats were compared after continuous (72 consecutive h) exposure to normobaric hypoxia or normoxia after the vasodilator naftidrofuryl or saline solution had been given intraperitoneally for 30 consecutive days. The maximum rats (Vmax) of the following enzyme activities in the crude extract and/or the crude mitochondrial fraction of each muscle specimen were evaluated for: the anaerobic glycolytic pathway (hexokinase, phosphofructokinase, pyruvate kinase, and lactate dehydrogenase), the tricarboxylic acid cycle (citrate synthase, and malate dehydrogenase), the electron transfer chain (cytochrome oxidase), and the NAD+/NADH redox state (total NADH cytochrome c reductase). The significance of differences between the enzyme activities at different ages or under different experimental conditions in the two tissue preparations of the two muscles were determined by ANOVA. MCA and ETA2 were used to evaluate the net effects of the experimental conditions. First, aging did not seem to affect the soleus and gastrocnemius muscles in the same way. In the gastrocnemius muscle, the major changes were seen in enzymes of the glycolytic pathway, in the crude extracts. In the soleus muscle, the more striking changes in enzyme activities as a function of aging were found in the crude mitochondrial fraction. We also found that hypoxia caused more important changes in 12-month-old rats than in those of other ages (especially the enzyme activities of the gastrocnemius muscle). Naftidrofuryl modified the effects of hypoxia only sometimes and further investigations are necessary before we can draw any conclusions about the pharmacological activity of naftidrofuryl in hypoxia.

Aging↗
PubMed1990

Measuring costs and financial benefits in randomized controlled trials.

Economic assessment can be incorporated into clinical trials to evaluate and compare the costs and benefits of different health care programs. In this article the three main types of evaluation are discussed: cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis. The measurement of direct and indirect costs is described and specific examples are quoted. Full economic analyses are given for the use of naftidrofuryl in the treatment of acute cerebral hemisphere infarction and the use of auranofin in the treatment of rheumatoid arthritis. Economic evaluation is seen to be justified whenever a more expensive treatment is expected to produce greater benefit. Such analyses should consider quality of life and health status, as well as the more easily identifiable outcomes.

Arthritis, Rheumatoid↗
PubMedDate not supplied

[Electrophysiological observations on seizure activity provoked by an intracarotid injection of Naftidrofuryl (author's transl)].

Three seconds after 0.08 g of Naftidrofuryl administered through the right carotid artery during an operation for carotid stenosis a right temporal sharp wave discharge occurred followed by diffuse polyspike activity occurring every 3to4 seconds with concomitant myoclonus. Rare episodes of this type are recorded in the literature when it has been used in neuroradiology. The authors state this agent should be forbidden by intracarotid injection.

Carotid Artery Diseases↗
PubMed1992

Praxilene (naftidrofuryl oxalate) as an alternative for the augmentation of femoro-distal bypass blood flow.

In 30 patients undergoing femoro-distal bypass the effect of papaverine and praxilene on blood flow in the graft was measured. The mean resting flow was 129 ml min-1 (range: 91-167) and after papaverine was 202 ml min-1 (142-262) and after praxilene was 205 ml min-1 (143-267). Praxilene has a similar effect to papaverine in the augmentation of blood flow, and further investigation is needed to see if long-term praxilene administration might improve graft survival.

Adult↗