Hypolipidaemic properties of a new tetralin derivative (CIBA 13,437-Su)

Hess, R.; Bencze, W. L.

doi:10.1007/bf02144360

Cited by 47 publications

(14 citation statements)

References 17 publications

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“…There was a 31% lower serum triglyceride concentration in naturally occurring hypertriglyceridemic female rats treated orally with SU-13,437 for 14 days compared to littermate controls receiving vehicle only. The serum triglyceride response observed in this study was similar to that observed in previous studies with normal (8,9,10,13) and fructose-induced hypertriglyceridemic (8,10) rats, and in humans with the Fredrickson-Lees-Levy phenotypes II, III, IV and V (11,12). Serum cholesterol levels were not affected by 437 in this study, in agreement with previous studies in Charles River rats by Best and Duncan (9,13).…”

Section: Discussionsupporting

confidence: 90%

“…The prevalence of familial hyperlipoproteinemias (1)(2)(3)(4) as well as the direct relationship between hyperlipidemia and atherosclerosis in the human population (4-7) has indicated a need for blood lipid lowering compounds. The compound 2-methyl-2-[p- (1,2,3,4- man (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). However the study of this compound in experimental animals having abnormal lipid patterns has been limited.…”

Section: Introductionmentioning

confidence: 99%

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The hypolipidemic effect of SU‐13,437 in rats with natural endogenous hypertriglyceridemia

Lenz

Fleischman

1971

Lipids

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The oral administration of 25 mg 2‐methyl‐2‐[p‐(1,2,3,4‐tetrahydro‐1‐naphthyl)‐phenoxy] propionic acid (SU‐13,437) per kilogram body weight per day in two‐month‐old female rats with naturally occurring hypertriglyceridemia resulted in a 31% decrease (P<0.01) in the serum triglyceride concentration after 14 days of treatment, compared with littermate controls receiving diluent (Polyethylene glycol‐300) only. Phospholipid, cholesterol, free fatty acid, glucose, red blood cell and white blood cell concentrations were similar in the blood of treated and control animals after 14 days of treatment. Liver total and relative weight was increased as a result of SU‐13,437 treatment (P<0.01). The liver total lipid concentration per 10 gm liver decreased (P<0.05) due to a decrease in triglyceride (P<0.01), cholesterol (P<0.01), and free fatty acid (P<0.05) concentration following treatment. The relative liver glycogen concentration was elevated in treated rats at 7 (P<0.01) and 14 (P<0.05) days of treatment.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

The hypolipidemic effect of SU‐13,437 in rats with natural endogenous hypertriglyceridemia

Lenz

Fleischman

1971

Lipids

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“…Recently, several new compounds of this class have been reported to show a lipid-low ering effect in rats and humans at a smaller dose than that required for clofibrate, but one of the general biological features of these compounds is that there is a marked hepatome galic effect in parallel with the hypolipidemic activity in the rodent (3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

Hypolipidemic Effect of a New Aryloxy Compound, S-8527, in Experimental Animals

Suzuki

Aono

Nakatani

1974

Japanese Journal of Pharmacology

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Abatract-The hypolipidemic action of 1,1-bis [4'-(l"-carboxy-1"-methylpropoxy)phenyl] cyclohexane (S-8527) was studied in rats, mice and rabbits under various ex perimental conditions to compare the effects with those of clofibrate. Oral ingestion of S-8527 to normal rats for 7 days lowered serum triglycerides and cholesterol by about 27% at 1 mg/kg and 20% at 3 mg/kg, respectively. The hypolipidemic effect of S-8527 was considered to be twenty to thirty times more potent than that of clo fibrate but a hepatomegalic effect of S-8527 was not observed at its effective dose ranging from 1 to 30 mg/kg. S-8527 at 3 mg/kg decreased liver triglyceride concen tration by about 20% but the decrease of triglyceride concentration was not ob served in clofibrate treated groups. Liver cholesterol concentration was not decreased with any of the doses of S-8527 while clofibrate decreased liver cholesterol concen tration by about 20% at 300 mg/kg. However, there were no differences in total content of cholesterol in liver between S-8527 and clofibrate treated groups. With Triton injected rats, a single oral dose of 100 mg/kg of S-8527 depressed the increase of serum triglycerides by about 50% while clofibrate did not. In glycerol-fed rats, S-8527 decreased serum and liver triglycerides more effectively than clofibrate, and in normal mice and cholesterol-fed mice, S-8527 was found to be more active than clo fibrate, however the hepatornegalic effect of S-8527 was less than that of clofibrate. Hypolipidemic effects in rabbits were not observed with either S-8527 or clofibrate.During a course of studies on hypolipidemic activity of various compounds synthe sized in our laboratory, we found that a new aryloxy compound, 1,1-bis [4'-(1 "-carboxy 1 "-methylpropoxy)phenyl] cyclohexane (S-8527) caused a marked decrease in serum lipids level at a smaller dose than that required for clofibrate and that there was a less hepatic effect at the effective dose in rats (1, 2). As studies concerning the dose-response relation ship in a wider range of doses of S-8527 were not included in the previous report (1), we do so herein.Recently, several new compounds of this class have been reported to show a lipid-low ering effect in rats and humans at a smaller dose than that required for clofibrate, but one of the general biological features of these compounds is that there is a marked hepatome galic effect in parallel with the hypolipidemic activity in the rodent (3-7).In the present study, an elucidation of the dose=response relationship for hypolipi demic activity of S-8527 in normal rats and its effect on hyperlipidemia induced by Triton injection, cholesterol feeding and glycerol loading in rats and mice are given. Hypolipidemic activity of S-8527 in normal mice and rabbits is also investigated.

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“…Mais, si ce mécanisme explique bien l'augmentation de la sensibilité aux antivitamines K, qu'on observe avec certains médicaments de la série (mais non tous), il explique mal leur action hypolipidémiante. En effet, l'augmen tation de la concentration de thyroxine au niveau du foie, qui pourrait lui être imputée selon T h o r p [25] n'est pas la cause de l'hypolipidémie due au médicament, car elle survient même chez les animaux thyroïdectomisés [13], pour ne citer que l'un des nombreux faits qui ne cadrent pas avec cette théorie. D'autre part, s'il est évident que les agents chimiques de la série du Clofibrate, comme bien d'autres, ont une action sur la cellule hépatique, il ne semble pas qu'elle puisse expliquer la totalité de leurs effets hypolipidémiants.…”

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Transport sanguin et mode d’action d’un médicament hypolipidémiant apparenté au Clofibrate: Le G P 45.699

Beaumont¹,

Dachet²,

Beaumont³

et al. 1971

Ann Nutr Metab

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G P 45.699 is a chemical hypolipidemic agent related to Clofibrate. The present study, achieved in man during a clinical assay, shows that the drug, after its intestinal absorption, is carried in blood by serum albumin, and also by low density lipoproteins, chiefly density 1.006–1.063 lipoproteins. In 4 normal subjects, the drug is found to be bound to albumin for 93–98%; to low density lipoproteins for only 2–6%. But when molecular weights are considered, the mole ratio of the drug per mole of albumin is less than 1, whereas per mole of lipoprotein it reaches 13 and even 25. Similar results were obtained in 4 hyperlipidemic subjects. This ability of low density lipoproteins to transport G P 45.699 in vivo was confirmed in vitro by the ability of purified β lipoproteins to bind the drug in saline. The presence of the drug on low density lipoproteins allows a new hypothesis concerning the hypolipidemic action of G P 45.699 and of related chemical compounds, Clofibrate being the best known. According to this hypothesis, the drug when binding with peptide B (apo-β-lipoprotein) within the mucosal cell, would reduce its ability to bind and transport triglycerides and cholesterol. A direct interaction between the drug and lipoproteins would fit better with its effects on lipidemia. Its interaction with albumin being responsible for some other effects, such an interference with several antivitamine-K anticoagulants.

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Hypolipidaemic properties of a new tetralin derivative (CIBA 13,437-Su)

Cited by 47 publications

References 17 publications

The hypolipidemic effect of SU‐13,437 in rats with natural endogenous hypertriglyceridemia

The hypolipidemic effect of SU‐13,437 in rats with natural endogenous hypertriglyceridemia

Hypolipidemic Effect of a New Aryloxy Compound, S-8527, in Experimental Animals

Transport sanguin et mode d’action d’un médicament hypolipidémiant apparenté au Clofibrate: Le G P 45.699

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