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At least 109 records · Page 6Linked to original sources
PubMed1971

Clinical evaluation of perhexiline maleate in patients with angina pectoris.

This paper reports a double-blind trial of a new antianginal drug, perhexiline. Fifty-five patients suffering from angina pectoris were studied for periods of 12 or 24 weeks in a cross-over comparison against a placebo in four centres in the United Kingdom and Ireland. Perhexiline was effective in most patients as judged by reducing the number of anginal attacks in 84% and the consumption of glyceryl trinitrate tablets in 64%. The major side effect, dizziness, noted in one-third of the patients, may be dose/body-weight related. Perhexiline is a valuable new agent for the treatment of patients with angina, especially those who do not respond to other antianginal agents.

Adult↗
PubMed1981

Lipid and lysosomal enzymes in human fibroblasts cultured with perhexiline maleate.

To understand the mechanism of the lysosomal lipid storage induced by perhexiline maleate, we performed simultaneous lipid analysis and lysosomal enzymes determinations. Human fibroblasts were cultured for 5 days in the presence of perhexiline maleate at a concentration of 2 micrograms/ml of culture medium. Lipid analysis showed that those non toxic levels determined the same changes as seen with higher concentrations of the drug (Hauw et al. 1980) i. e. increase of cholesterol and of all major phospholipids. Qualitative phospholipid pattern was not markedly changed. Lysosomal enzymes activities were not modified with the exception of sphingomyelinase which was reduced to 12% of its normal level.

Cells, Cultured↗
PubMed1981

Antiarrhythmic evaluation of verapamil, nifedipine, perhexiline and skf 525-A in four canine models of cardiac arrhythmias.

Verapamil, nifedipine, perhexiline and SKF 525-A (2-diethylaminoethyl-2,2-diphenylvalerate . HCL) were evaluated for cardiac antiarrhythmic activity by assessing their effectiveness in increasing left ventricular fibrillation threshold (FT) and antagonizing ouabain-induced arrhythmias (OA), 24 h post infarction arrhythmias (CLA) and aconitine-induced atrial arrhythmias. Calcium antagonistic doses (ID50) of each agent were approximated by intravenous titration of the amount of drug required to reduce the left ventricular contractile force by 50% in dogs pretreated with hexamethonium (10 mg/kg) to block autonomic reflexes. ID50 doses of calcium antagonists were found not to be universally effective in any single arrhythmia model while causing significant changes in heart rate, blood pressure and frequently producing death or convulsion. It is suggested that local anesthetic or 'class 1' action probably accounts for the antiarrhythmic effectiveness of SKF 525-A (7-20 mg/kg i.v.) in all four arrhythmia models and for perhexiline-induced increased FT and antagonism of CLA (15-20 mg/kg). Antiarrhythmic effectiveness of verapamil against OA may be due to calcium antagonism action.

Animals↗
PubMed2006

Metabolic therapeutics in angina pectoris: history revisited with perhexiline.

The ever-increasing burden of ischaemic heart disease and its common manifestation chronic angina pectoris calls for the exploration of other treatment options for those patients who despite the maximum conventional pharmacological and surgical interventions continue to suffer. Such exploration has led to the increasing use of new metabolically acting antianginal agents and the re-emergence of an old and somewhat forgotten pharmacological agent, perhexiline maleate. This review aims to update the cardiac nurse with knowledge to manage the care a patient receiving perhexiline maleate treatment and provide a brief review of three new metabolic agents: trimetazidine, ranolazine and etomoxir.

Acetanilides↗
PubMed1985

Investigations of long-term treatment with perhexiline maleate using therapeutic monitoring and electromyography.

Experience is reported with 41 patients taking perhexiline maleate for angina pectoris for periods of up to 70 months, while serum concentrations of the drug were monitored, and liver function tests and electromyographic tests were made before and during treatment. Severe side effects did not occur unless serum perhexiline levels were greater than 1.5 mg/L. The drug seems effective for prolonged dosage, and the monitoring of weight, liver function test results, and serum concentrations should prevent or reduce toxicity. A starting dose of 100 mg daily is recommended. The drug is not recommended for routine use in angina pectoris.

Adult↗
PubMed1979

Liver damage associated with perhexiline maleate.

Two patients who developed biochemical and histological evidence of hepatitis while taking the anti-anginal drug perhexiline maleate are described. The pathological changes were those of mild to moderate fatty change together with a hepatitis which resembled alcoholic hepatitis, including in one patient the presence of material which by light microscopy was indistinguishable from Mallory's alcoholic hyalin. However, the predominantly periportal location of this material contrasted with the centrilobular distribution of Mallory's hyaline. One patient showed, in addition, severe atypia of the hepatocytes which was still present in less pronounced form 10 weeks after stopping perhexiline. The other patient had advanced hepatic fibrosis.

Aged↗
PubMed1980

Perhexiline maleate toxicity on human liver cell lines.

When added to the culture medium of human liver cell lines, perhexiline maleate induced formation of numerous myeloid bodies containing unicentric or multicentric smooth membranes within a few days. The nine lysosomal enzyme activities studied, except for beta-galactosidase which decreased, remained unchanged. These results indicate that on cultured human liver cells perhexiline maleate has an effect similar to that described on hepatocytes of some patients treated with this drug and suggest that myeloid body formation is not due to impairment of lysosomal enzyme activities.

Adult↗
PubMed1980

Effects of oral perhexiline on canine myocardial flow distribution.

Perhexiline maleate at a dose of 400 mg three times daily for 2 days administered to normal dogs altered the relative regional transmural resistance so that during reduced coronary flow the endocardium:epicardium (endo:epi) ratio is increased. In the presence of acute myocardial infarction heart rate was significantly lower and the endo:epi ratio of perfused areas was increased when coronary flow was normal. A linear relationship was observed between the endo:epi ratio and the concentration of perhexiline in plasma, and its monohydroxyl metabolite in plasma. The results suggest that the mechanism of action of the drug is due to redistribution of a limited coronary flow.

Animals↗
PubMed1992

Golgi vacuolization and immunotoxin enhancement by monensin and perhexiline depend on a serum protein. Implications for intracellular trafficking.

Vacuole formation around the Golgi and immunotoxin enhancement induced by low doses of the ionophore monensin were inhibited by 50% human plasma (final concentration), whereas the lysosomal pH increase remained unaffected. Immunotoxin enhancement by the Ca2+ antagonist perhexiline was also inhibited by plasma. The inhibiting factor was present in different species and highly concentration-dependent. After purification on DEAE- and CM-Sepharose it showed a heterogeneous distribution between 45 and 50 kDa, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, an extreme isoelectric point near 3.5, and binding to wheat germ agglutinin-Sepharose. Maximum inhibition was found in the lower molecular mass fraction of 45 kDa. The 50-kDa fraction, although showing immunological identity reactions, remained almost inactive. The simultaneous inhibition of morphological alterations and the enhancement of immunotoxin activity by the highly enriched protein provides a first direct link between both events. Apart from a role of this serum glycoprotein on in vivo inhibition of immunotoxin enhancement, its ability to maintain normal intracellular trafficking in the presence of blocking agents, such as monensin and perhexiline, suggests a more fundamental role in the regulation of these mechanisms.

Biological Transport↗
PubMed1991

[Effects of N-ethyl perhexiline on His bundle electrogram in rabbits].

N-Ethyl perhexiline (NEP), a drug was synthesized for the first time by Department of Organic Chemistry, Faculty of Chemistry, Beijing University. The effects of NEP on the A-V conduction and intra ventricular conduction were studied in the anesthetized rabbits by recording His bundle electrogram (HBE) and electrocardiogram (ECG). NEP 3 mg.kg-1 iv prolonged A-H, P-R and R-R intervals. When NEP 6 mg.kg-1 was given, the above changes became more significant, with A-H interval from 52 +/- 7 to 65 +/- 9 ms, P-R interval from 65 +/- 6 to 76 +/- 8 ms, R-R interval from 207 +/- 9 to 230 +/- 9 ms, and H-V interval from 19 +/- 3 to 23 +/- 5 ms. The effects of NEP were similar to that of perhexiline, but the effects of NEP on A-H and P-R intervals were stronger. NEP 6 mg.kg-1 iv antagonized shortening effect of nicotinamide 0.5 g.kg-1 on A-H interval in rabbits. When isoproterenol 10 micrograms.kg-1 was given 3 min after NEP 6 mg.kg-1 iv, the A-H interval prolongation induced by NEP was greatly inhibited. The results suggested that the prolongation effects of NEP on A-H, P-R and R-R intervals would be the results of its calcium-channel blockade.

Animals↗
PubMedDate not supplied

[Polyneuritis after use of perhexiline maleate: quantimetric and ultrastructural study (author's transl)].

The authors record a new case of polynevritis through a prolonged use of perhexiline maleate. The acute neurological episode occurred 14 months after the beginning of the treatment when the daily doses had been raised to 600 mg for 2 months. The biopsy of the peripheral nerve was carried out only 27 months later as the posology was brought down to 200 mg and the clinical symptomatology had almost completely diminished. This probably accounts for the unusual aspects observed on semi-thin and ultrathin sections: a very remarkable reduction of the number of myelinated fibers and the severity of the phenomena of Wallerian degeneration, contrasting with the rarity of intra-cytoplasmic multilamellar schwannian inclusions, classically observed in the course of polynevritis caused by perhexiline maleate. The direct toxic action of the drug upon the neuron has been discussed.

Humans↗
PubMed1983

[Study of thesaurismosis induced by perhexiline maleate. Confirmation of experimental data].

Perhexiline maleate is an amphiphilic molecule. Along with many other drugs it is responsible for experimental and, in some instances, clinical lipidoses. Sphingomyelinase deficiency has been evidenced in cell cultures incubated with perhexiline maleate. We describe the occurrence of a similar defect in a patient. The disturbances in the phospholipid turnover which are responsible for the thesaurismosis may originate in the sphingomyelinase deficiency.

Cerebellar Ataxia↗
PubMed1984

Extracellular potassium concentration; perhexiline and SKF-525A on the action of ouabain in isolated self-beating rat auricles.

The influences of different extracellular K+ concentrations and of blockers of potassium and calcium movements through cell membranes (perhexiline and SKF-525A) on the effects of ouabain on self beating isolated rat atria, both "non toxic" (positive inotropism without changes in contractile frequency or resting tension) and "toxic" (positive chronotropism, negative inotropism, contracture, arrhythmia), were explored. Decreasing extracellular K+ from 6 to 3 mM potentiated both the positive inotropic influences as well as the "toxic" effect of ouabain, whereas, increasing K+ from 6 to 8 mM delayed but potentiated the onset of the "non toxic" influences of the drug and abolished its "toxic" responses. Perhexiline and SKF-525A, sensitized the tissue to the "non toxic" effects of the glycoside, attenuated contracture but increased the positive chronotropic action. The aforementioned results suggest that factors which modify potassium environment (i.e., variable extracellular potassium concentration and ion-flux blocking agents) resulted in significant modification of the effect of ouabain on isolated rat myocardium.

Animals↗
PubMed1983

Ultrastructural alterations in peripheral nerve trunks of rats subchronically treated with chlorphentermine or perhexiline.

The present study deals with the effects of two lipidosis-inducing drugs (chlorphentermine and perhexiline) upon the ultrastructure of large nerve trunks (sciatic and plantar nerves) of adult rats. Subchronic oral administration of high doses of either drug led to comparatively mild lipidosis-like alterations in Schwann cells and in other cell types of both nerve trunks. In addition, plantar nerves, and more rarely sciatic nerves, showed some unspecific lesions such as myelin whorls and ovoids within the outer Schwann cell cytoplasm, intra-axonal accumulations of polymorphous material, and single degenerating fibres. The pathogenetic mechanisms responsible for the non-specific lesions remain to be elucidated. Chlorphentermine was, in all respects, more potent than perhexiline. In general, the drug-induced lesions developing in the fibres of large nerve trunks were less dramatic when compared a) with the severe lipidosis known to occur in neuronal perikarya, and b) with the severe alterations known to develop in preterminal or terminal axon portions of rats kept under similar experimental conditions.

Animals↗
PubMed1977

[Hypoglycemia in 2 patients treated with perhexiline maleate].

Hypoglycaemia occurred in two patients treated with perhexiline maleate. The responsibility of the medication is discussed in each case. Blood insulin levels were increased. Blood perhexiline levels decreased very rapidly in the first patient, though much more slowly in the second.

Aged↗
PubMed1977

[Hepatic overload of gangliosides after perhexiline maleate. Morphological and biochemical course (author's transl)].

A 72 years old man treated with perhexiline maleate (400 mg during 15 months) complained of skin rash, sensitive neuropathy, liver damage and mild renal insufficiency. Clinical status improved when the treatment was stopped, but liver size and renal status remained inchanged. Liver biopsy were performed at 0,6 and 15 months after the end of treatment. Inflammation and hepatocyte necrosis, seen on the first specimen, disappeared latter. Steatosis and voluminous, swollen, foamy liver seen were present in the three biopsies. Sclerosis had increased in the last one in spite of treatment arrest. Histochemical study exhibited liver storage of triglycerides, fatty acids, phospholipids, and gangliosides. Cytoplasmic glycogen was increased and some nuclei were glycogenated. Enzymatic pattern suggests a minor form of type I glycogen storage or increased neoglycogenesis. Perhexiline relation to this complex liver storage is discussed.

Aged↗
PubMed1978

Perhexiline neuropathy: a clinicopathological study.

Five patients developed a mild to severe polyneuropathy while under treatment with perhexiline maleate, a drug used in long-term treatment of angina pectoris. Recovery took place within a few months after drug withdrawal. We performed qualitative and quantitative light and electron microscopical studies, including teased fiber preparations, in different patients; 16 to 90% of the fibers showed segmental demyelination, an unusual feature in drug-induced neuropathies, and 3 to 20% were undergoing wallerian degeneration. Severe loss of myelinated axons was noted in all 5 patients. In these patients clinical symptoms occurred only when a great number of fibers had already been lost and most of the surviving fibers showed demyelination.

Aged↗