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At least 19 recordsLinked to original sources

PubMed1996

Effects of delayed treatment with nafronyl oxalate on microsphere embolism-induced changes in monoamine levels of rat brain regions.

1. The present study was undertaken to examine the effects of delayed treatment with nafronyl oxalate (nafronyl), a cerebral vasodilator, on monoamine neurotransmitters of brain regions in the microsphere-embolized rat. 2. Microsphere embolism was induced by injecting 900 microspheres with a diameter of 48 microns into the right internal carotid artery of rats. Microsphere-embolized rats were treated with nafronyl, 15 mg kg-1, i.p., twice daily from the first to the 5th day. Levels of monoamines and their metabolites in the cerebral cortex, striatum, and hippocampus were measured on days 3 and 5 after the operation by a high-performance liquid chromatograph with electrochemical detection. In vivo tyrosine or tryptophan hydroxylation was estimated by measurement of the accumulation of 3, 4-dihydroxyphenylalanine or 5-hydroxy-1-tryptophan after administration of 3-hydroxybenzylhydrazine dihydrochloride, an inhibitor of aromatic L-amino acid decarboxylase. 3. Microsphere embolism induced decreases in dopamine, noradrenaline and 5-hydroxytryptamine in three brain regions of the right hemisphere on days 3 and 5. In the left hemisphere, the monoamines were reduced, but to a lesser degree than in the right hemisphere. On days 3 and 5, the decrease in the monoamines of the right hemisphere was attenuated by nafronyl treatment except for noradrenaline on day 3. The decrease in the monoamines levels in the left hemisphere was almost completely prevented by nafronyl treatment. 4. On day 3 after microsphere embolism, in vivo tyrosine and tryptophan hydroxylation was lower than the pre-embolic value in all three brain regions. Treatment of the embolized rats with nafronyl significantly attenuated the decrease in in vivo tyrosine and tryptophan hydroxylation in the ipsilateral hemisphere, but not hippocampal tryptophan hydroxylation. 5. The results suggested that treatment with nafronyl improves or attenuates changes in monoamine neurotransmitter metabolism of the brain regions impaired by microsphere embolism. The mechanisms underlying this effect may be attributed to preservation of the ability to synthesize monoamines when the brain is ischaemic or oligaemic.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1981

Prediction of stability in pharmaceutical preparations XVIII: application of high-pressure liquid chromatographic assays to study of nafronyl stability and bioanalysis.

Specific, sensitive, reversed-phase high-pressure liquid chromatographic assays of nafronyl (I) and its acidic metabolite and hydrolysis product (II) were developed in aqueous solutions and in biological fluids with sensitivities of 100 ng/ml using butacaine as the internal standard and spectrophotometric detection of 224 nm. Heparinized plasma can be analyzed easily in the organic phase immediately after acetonitrile denaturation. Both I and II can be extracted with haloalkane solvents, and the extracts are evaporated, reconstituted, and assayed in a minimal amount of acetonitrile. Conditions are presented that minimize the interference of II and extracted plasma components. The assay was used to determine the stability of nafronyl in aqueous solutions, to establish its log k-pH profiles at various temperatures, and to evaluate the Arrhenius parameters. Nafronyl is hydrolyzed by specific hydrogen-ion (15.2 kcal/mole) and hydroxide-ion (7.72 kcal/mole) catalysis of the neutral species and specific hydroxide-ion catalysis (5.91 kcal/mole) of the protonated species. The pH of maximum stability is 3.0, and pH 5.4 is the maximum that can be tolerated at 30 degrees, with a 10% solvolysis in 3 years. The half-life of nafronyl at 30 degrees was 7 days at pH 7, 12 hr at pH 10, and 21 min in 0.5 N NaOH. Since nafronyl has a half-life of 3.2 hr in heparinized dog plasma at 25 degrees, blood samples for pharmacokinetic studies of nafronyl must be assayed immediately after sampling. The partition coefficients of I and II determined as functions of pH permit the extraction of both compounds at pH 4.5, but only I can be extracted at pH values above 9.5.

Animals↗

PubMed1999

Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis.

BACKGROUND: There is no consensus on the efficacy of physical training, smoking cessation, and pharmacological therapy (pentoxifylline or nafronyl oxalate) in the treatment of patients with intermittent claudication at Fontaine stage II of disease. METHODS: A MEDLINE and manual search was used to identify relevant publications. Uncontrolled or retrospective studies, double reports, and trials without clinically meaningful outcomes were excluded. Included studies were graded level 1 (randomized and double- or assessor-blind), level 2 (open randomized), or level 3 (nonrandomized). Pain-free and total walking distance were the main outcomes considered; when feasible, end-of-treatment results were combined with appropriate meta-analytical procedures. RESULTS: In 5 level 2 studies, physical training increased pain-free and total walking distance significantly (139.0 m [95% confidence interval {CI}, 31.0 to 246.9 m] and 179.1 m [95% CI, 60.2 to 298.1 m], respectively). In a level 3 study, smoking cessation resulted in a nonsignificant increase in total walking distance of 46.7 m (95% CI, -19.3 to 112.7 m). In 6 level 1 studies, pentoxifylline increased both pain-free and total walking distance by 21.0 m (95% CI, 0.7 to 41.3 m) and 43.8 m (95% CI, 14.1 to 73.6 m), respectively. In 4 level 1 trials, nafronyl significantly increased pain-free walking distance (58.6 m [95% CI, 30.4 to 86.8 m]) and total walking distance (71.2 m [95% CI, 13.3 to 129.0 m]). CONCLUSIONS: Physical training increased pain-free and total walking distance in level 2 studies. Only level 3 studies support the usefulness of smoking cessation. In level 1 studies, pentoxifylline and nafronyl increased pain-free and total walking distance, but the average effects were relatively small.

Clinical Trials as Topic↗

PubMed1984

Bioanalyses and pharmacokinetics of nafronyl in the dog.

Improved specific and sensitive reverse-phase HPLC assays of nafronyl (I) and its acidic metabolite and hydrolysis product (II) in biological fluids were developed with sensitivities of 3-6 ng/mL using fluorometric detection with 225 nm excitation and 330 nm emission wavelengths. There were no significant differences in the stabilities and assays of I and II in plasma obtained using heparin, citrate phosphate dextrose solution, EDTA, citrate, or oxalate as anticoagulant. Inordinately high membrane binding did not permit the quantification of the high plasma protein binding of I by ultrafiltration; its instability precluded the use of equilibrium dialysis. Plasma protein binding of II by ultrafiltration was 76.4% and was not concentration dependent. The apparent red blood cell-plasma partition coefficients for I and II were 2.00 and 0.49, respectively, with almost all anticoagulants; the red blood cell-plasma water partition coefficient for II was 2.08 when corrected for plasma protein binding. Thus, both I and II had erythrocyte binding sites in addition to simple volume partitioning. Only heparin-treated blood gave anomalously low erythrocyte-plasma partition coefficients, indicating that heparin inhibited the partitioning of I and II into red blood cells from plasma water. The total body clearance of nafronyl (I) referenced to total plasma concentration [1295 +/- 65 (SEM) mL/min] was dose independent (35-70-mg range) and showed biphasic plasma half-lives (intravenous) of 12 and 100 min. Only 34% of the nafronyl appears as systemically circulating II in the plasma. Apparent volumes of distribution similarly referenced were 39.8 and 163 L for the central compartment and total body, respectively. Renal clearances referenced to total plasma concentration were 8.3 and 0.18 mL/m for I and II, respectively. The respective total urinary excretions of I, II, and the glucuronide of II (III) were 0.48, 0.021, and 0.32% of the administered intravenous doses. The respective total urinary excretions of I, II, and III for a bile-cannulated dog were 0.005, 0.16, and 0.40%. The total body clearance of intravenously administered II was 225 mL/min, with a renal clearance of 0.057 mL/min referenced to total plasma concentration. The respective total urinary excretions of II and III were 0.027 and 0.44% of the intravenous dose of II. Respective plasma half-lives of II (intravenous) were 2.5, 10.9, and 225 min. The apparent volume of distribution referenced to total plasma concentration was 2.2 L (9.1 L referenced to plasma water concentration). The apparent overall volume of distribution referenced to plasma concentration was 73 L.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1998

Determination of nafronyl in pharmaceutical preparations by means of stopped-flow micellar-stabilized room temperature phosphorescence.

The stopped-flow mixing technique was applied to micellar-stabilized room temperature phosphorimetry by measuring the fast appearance of the phosphorescent signal yielded by nafronyl in the presence of sodium dodecyl sulfate and thallium nitrate. This mixing system diminishes the time required for the deoxygenation of micellar medium by sodium sulfite, allowing a kinetic curve that levels off within only 5 s to be obtained. Phosphorescence enhancers thallium(I) nitrate, sodium dodecyl sulfate and sodium sulfite were optimized to obtain maximum sensitivity and selectivity. A pH value of 10.5 was selected as adequate for phosphorescence development. Two rapid, straightforward and automatic methods were proposed using the slope and amplitude of the kinetic curve, which are directly proportional to the nafronyl concentration, as analytical parameters. Calibration graphs were linear for the concentration range from 30 to 600 ng ml-1. Praxilene, the only commercial formulation containing nafronyl, was analysed by both proposed methodologies. Suitable recovery values were obtained.

Humans↗

PubMedDate not supplied

Metabolism of nafronyl in man.

The metabolism of nafronyl (I) has been studied in man. In addition to small amounts of the parent compound, three acidic metabolites were extracted from urine. The chemical structures of all metabolites were determined by using mass spectrometry and [1H]-NMR spectroscopy as tetrahydro-beta-(1-nephthalenylmethyl)-2-furanpropionic acid (II) and two stereoisomers of 3-(1-naphthalenylmethyl)-tetrahydrofuran-2-one-5-propionic acid (III, IV). The biodegradation products III and IV are formed after oxidation of the tetrahydrofuran system in II, hydrolytic ring opening of the gamma-butyrolacton and a subsequent formation of a gamma-butyrolacton ring with the second carboxyl group. The three metabolites represent the major fraction of unconjugated products in the urine of man after administration of nafronyl.

Adult↗

PubMed2000

Facile and selective determination of the cerebral vasodilator nafronyl in a commercial formulation by heavy atom induced room temperature phosphorimetry.

This paper presents a facile and selective method for the determination of the pharmaceutical compound nafronyl using heavy atom induced room temperature phosphorimetry (HAI-RTP) as analytical technique. The determination was performed in potassium iodide 1.6 M and sodium sulphite 0.002 M at a measurement temperature of 20 degrees C. The phosphorescence intensity was then measured at lambda(exc) = 292 nm and lambda(em) = 524 nm. Phosphorescence was fully developed instantly, obtaining a linear concentration range between 2.7 and 250 ng ml(-1) with the detection limit of 2.7 ng ml(-1), an analytical sensitivity of 5.1 ng ml(-1) and a standard deviation of 2.17%, at a 150 ng ml (-1) concentration level. The proposed method has been satisfactorily applied to the unique Spanish commercial formulation containing nafronyl at a 100 mg level per capsule. The recovery was 108%, with a 1.7%, standard deviation of the analytical measurement. The method has been validated using standard addition methodology.

Calibration↗

PubMed1982

Effect of nafronyl on lactate and pyruvate in the cerebrospinal fluid of patients with senile dementia.

In a single-blind study, 12 men (mean age 63 years) with senile dementia were given nafronyl in a dosage of 100 mg eight times daily for a week, followed by 100 mg four times daily for 12 weeks. Rigorous clinical, laboratory and psychometric assessments revealed no toxicity and no significant effects on vital functions. In the cerebrospinal fluid, the ratio of lactate to pyruvate decreased--a finding consistent with an increase in the aerobic metabolism of glucose.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1982

The usefulness of naftidrofuryl in severe peripheral ischaemia--a symptomatic assessment using linear analogue scales.

The effect of Naftidrofuryl (Nafronyl) on the symptoms of severe peripheral vascular disease has been studied in 40 hospital inpatients. Assessment of ischaemic symptoms and of symptoms which may occur with any type of chronic pain was made using a linear analogue system. Patients treated with naftidrofuryl showed a significant symptomatic improvement compared to patients treated without vasoactive drug therapy. These results show that this drug has a useful place in the treatment of severe ischaemic symptoms during assessment for vascular reconstruction and in those patients found to be unsuitable for limb-salvage operations.

Aged↗

PubMed1982

Heterogeneity of biochemical actions among vasodilators.

Thirty-four vasodilators were screened in several in vitro biochemical assays related to smooth muscle excitation-contraction coupling, binding to beta 1-,beta 2-, and alpha-adrenergic receptors, inhibition of phosphodiesterase activity, and antagonism of calcium accumulation. Isoproterenol and perhexiline only exhibited binding to beta-adrenergic sites. Ergocryptine, tolazoline, and amotriphene only bound to alpha-adrenergic receptors. Leniquinsin, papaverine, proquazone, dioxyline, hoquizil, quazodine, and theophylline were active only as phosphodiesterase inhibitors. Isoxsuprine, nylidrin, and bencyclane bound to alpha- and beta-receptors. Pentoxifylline bound to beta 1-sites and inhibited phosphodiesterase. Cyclandelate bound to beta 2-sites and blocked calcium accumulation. Cinnarizine and flunarizine antagonized calcium accumulation and bound to alpha-sites. Prazosin bound to alpha-sites and inhibited phosphodiesterase. Ethaverine and dipyridamole were inhibitors of phosphodiesterase and calcium accumulation. Nafronyl bound to beta 2- and alpha-sites and antagonized calcium accumulation. Mebeverine bound to beta 2- and alpha-receptors and inhibited phosphodiesterase activity and calcium accumulation. Verapamil bound to alpha-sites, and blocked phosphodiesterase and calcium accumulation. Quinazosin bound to beta 2- and alpha-receptors and antagonized both phosphodiesterase activity and calcium accumulation. Vasodilators that were inactive in all assays included niacin, nicotinyl alcohol, inositol nicotinate, amyl nitrite, sodium nitroprusside, diazoxide, hydralazine, and protoveratrine. Vasodilators should not be considered as a single drug class since they act on various mechanisms related to coupling of neuronal excitation to muscular contractility.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1986

Drug therapy of Alzheimer's disease: realistic or not?

Drug therapy of Alzheimer's disease is either symptomatic, directed against behavioral manifestations, or specific, presumably directed against some hypothetical pathogenetic mechanism. Symptomatic treatment involves the use of antipsychotic drugs, alone or combined with benzodiazepines, to curb disturbed behavior, restore a normal sleep-wake cycle and improve self-care. Antidepressants can be used cautiously when indicated. Specific treatment has employed many different drugs over the years, including stimulants, cerebral vasodilators, drugs for certain hypothesized causes of the disorder, and drugs assumed to enhance metabolism of the brain, or to protect it against various insults. Of the metabolic enhancing drugs, ergoloid mesylates, nafronyl and piracetam are of the greatest current interest. Ergoloid mesylates have been the most extensively studied, but many questions about this drug, such as its mechanism of action, its proper dose, the proper duration of treatment, and the proper goals of treatment, remain unanswered. Symptomatic treatment is essential, both of the sake of patients and those who attend them. Specific treatment is more controversial. If specific treatment is warranted, ergoloid mesylates might be a reasonable first-choice. A number of experimental approaches aimed at enhancing deficient neurotransmission, or remedying deficient neuropeptides, are currently being investigated. Meanwhile, it is realistic to attempt to do the best one can for the afflicted patients.

Alzheimer Disease↗

PubMed1988

Drugs affecting the inner ear. A review of their clinical efficacy, mechanisms of action, toxicity, and place in therapy.

Many drugs have a site of action within the inner ear. The list includes therapeutic, diagnostic and ototoxic agents. Therapeutic agents are most useful in cases of infections, endolymphatic hydrops, vascular insufficiency, vertigo of peripheral origin, autoimmune disease, otosclerosis (otospongiosis), sudden hearing loss and tinnitus. For infections, the most widely used anti-microbial agents are the penicillins and cephalosporins. There are no antiviral agents that have been proven useful for inner ear viral infections. However, steroids have been of some value for controlling some of the sequelae. Steroids have also been useful in conjunction with ampicillin in cases of syphilitic hearing loss. In cases of endolymphatic hydrops, the diuretics chlorthalidone, hydrochlorothiazide and acetazolamide have been useful. When diuretic and diet therapy cannot control endolymphatic hydrops, ototoxic drugs such as streptomycin have been used. In cases of vascular insufficiency within the inner ear, vasodilators such as carbon dioxide, papaverine, buphenine (nylidrin), naftidrofuryl (nafronyl) and thymoxamine have been recommended, but their true efficacy is questionable. Some success with betahistine has been achieved but the mechanism of this drug's action may be other than vasodilatation. Vertigo is best controlled with antihistamines and anticholinergics and with certain calcium channel blockers. Autoimmune inner ear disease appears to respond to a combination of steroids and cyclophosphamide. Although controversial, current pharmacotherapy for otosclerosis includes sodium fluoride. Sudden hearing loss is treated with a 'shotgun' combination of drugs and/or bed rest. There are as yet no drugs which can be used to routinely reduce tinnitus although some medications may help the patient tolerate the problem. Lignocaine (lidocaine) is useful in diagnosing, and very evanescently reducing, tinnitus. Glycerin (glycerol) is useful in diagnosing endolymphatic hydrops and may at times transiently reduce tinnitus. The drugs most noted for their ototoxicity are the aminoglycoside antibiotics, certain diuretics, non-steroidal anti-inflammatory agents, certain anticancer agents and some miscellaneous chemicals. Some new research drugs are in clinical trials for tinnitus, hearing loss and vertigo, and the rational search for new otopharmacotherapeutic agents is increasing.

Ear, Inner↗

PubMed2002

[Applications of phosphorimetry in pharmaceutical analysis].

Applications of phosphorimetry including solid substrate phosphorescence, liquid medium phosphorescence, low temperature phosphorescence and phosphorescence sensors were reviewed in pharmaceutical analysis. The drugs involved here included the varieties of alkaloid, Chinese traditional medicine, tetracyclines, quinolone, riboflavin, anticancer medicine, naphazoline, naproxen, nafronyl dipyridamole and so on. Solid surface phosphorimetry is characterized by sample volume of microliter grade, simple and fast operation procedures in pharmaceutical analysis. The combination of liquid phosphorescence with flow injection analysis and chemosensing technique has good advantages in fast, continuous and on-line monitoring of medicines. Modified low temperature phosphorimetry still remains its high sensitivity and overcomes some disadvantages in the procedures. Phosphorimetry will be more widely applied to pharmaceutical analysis as the development of sensitive and quenching, energy transfer, derivative and immunization luminescence.

Alkaloids↗

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↗

PubMed2000

Intravenous naftidrofuryl for critical limb ischaemia.

BACKGROUND: Peripheral arterial disease affects 5% of men and women by late middle age. In approximately 25% of those affected the condition will progress to critical limb ischaemia (rest pain, ulceration and gangrene) within five years. The vasoactive drug naftidrofuryl is a serotononergic receptor antagonist which may be beneficial in the treatment of severe lower limb disease such as critical limb ischaemia. OBJECTIVES: To determine whether the vasoactive drug, naftidrofuryl, when administered intravenously is effective in alleviating symptoms and reducing progression of disease in patients with critical limb ischaemia. SEARCH STRATEGY: Randomised controlled trials were identified using the search strategy of the Peripheral Vascular Diseases Review group, including MEDLINE and EMBASE searches and reviewing reference lists in papers. In addition, publications were identified through pharmaceutical companies. SELECTION CRITERIA: All randomised controlled trials of critical limb ischaemia in which patients were randomly allocated to intravenous naftidrofuryl or control (either pharmacological, inert placebo or conservative therapy) were included. Patients with intermittent claudication were not eligible for inclusion. Trials were selected by one reviewer and checked independently. DATA COLLECTION AND ANALYSIS: Fifteen trials were identified, but eight were excluded because of poor methodology. The seven remaining trials involved a total of 229 participants from five different countries. The following outcomes were reported: pain reduction, rest pain/necrosis, progression of disease in terms of incidence of surgical reconstruction/amputation, mortality and side effects. On extraction of the data, odds ratios and weighted mean differences were estimated where appropriate. MAIN RESULTS: Treatment with naftidrofuryl tended to show reduction of pain evaluated by both analogue score and analgesic consumption, but the effect was statistically non-significant (weighted mean difference -0.42, 95% confidence interval -1.19 to 0.35). Similarly, improvement in rest pain or skin necrosis occurred, but these effects were also not significant. The effect on mean ankle systolic ankle pressure was inconclusive. REVIEWER'S CONCLUSIONS: Based on the results of these trials, it cannot be confirmed that intravenous naftidrofuryl is effective in the treatment of patients with critical limb ischaemia. However, these results were based on trials of generally low methodological quality which had only a small number of participants, the duration of treatment was extremely short and the methods varied between the trials. The wide range of endpoints effectively precluded any meaningful pooling of the results. Intravenous naftidrofuryl was withdrawn as a treatment for peripheral arterial disease in 1995 because of reported side effects.

Extremities↗

PubMedDate not supplied

Plasma concentrations and relative bioavailability of naftidrofuryl from different salt forms.

The relative bioavailability of the vasodilator naftidrofuryl from formulations containing its oxalate or citrate salt has been estimated using a specific HPLC assay, and a less specific fluorimetric assay, to measure plasma drug concentrations. The conclusions of the study were the same irrespective of the assay employed. The relative rate, but not the extent, of bioavailability of naftidrofuryl from the citrate salt (peak 1096 ng ml-1 at 0.76 h) was marginally greater (p = 0.003) than that from the oxalate salt (peak 922 ng ml-1 at 0.94 h). The degree of intersubject variability was similar after administration of either salt form. The mean half-life of naftidrofuryl was 1.8 h and its mean residence time was 2.5 h.

Adult↗

PubMed1980

A controlled trial of naftidrofuryl (Praxilene) in the treatment of intermittent claudication.

We present the results of a double-blind trial of naftidrofuryl (Praxilene) in the treatment of intermittent claudication. One hundred and twenty-eight patients were subjected to a standard walking test 3 and 6 months after treatment. There was no significant objective improvement attributable to the drug. Although both groups significantly increased their walking time to the onset of pain, those patients over 60 years old taking naftidrofuryl showed a significant improvement over their pretreatment walking times to onset of pain, whereas their controls did not.

Ankle↗

PubMed1980

The effect of naftidrofuryl (Praxilene) on intermittent claudication.

In a randomized double-blind controlled trial the effect of naftidrofuryl (Praxilene) 200 mg t.d.s., taken for 6 months, was compared with placebo in intermittent claudication. Whilst there was a significant subjective improvement regardless of age or treatment, patients over 60 on naftidrofuryl experienced a more rapid symptomatic relief than other patients. At six months this age group showed a significant improvement over the placebo group. There was no significnat objective evidence of improvement.

Aged↗