
Originally Posted by
BJJ
1
Efficacy and interactions of oxandrolone, halo-fenate and clofibrate in a factorial study on experimental acute nephrotic hyperlipidemia
GJ Schapel and KD Edwards
Nephrotic mixed hyperlipidemia may be associated with accelerated coronary artery disease. To investigate the response of experimental nephrotic hyperlipidemia to therapy, a 2(4) factorial study of sodium clofibrate and beta-benzalbutyrate, halofenate and oxandrolone (250, 150, 100 and 10 mg/kg/day, respectively) was carried out. Nephrotic syndrome was induced by a single i.p. injection of puromycin aminonucleoside (90 mg/kg) in 80 female white rats of average weight 160 g. Oxandrolone proved to be significantly hypotriglyceridemic in combined therapy (average fall, 38%; P less than .05), and also lowered serum total cholesterol and phospholipid concentrations (23% and 21% falls, P less than .01) and less than .05), due largely to synergistic interactions with clofibrate-like drugs. Hypocholesteremic effects (23 and 22% average falls) were also significant for halofenate (P less than .01) and clofibrate (P less than .05) . Serum triglyceride levels actually rose significantly (P less than .05) with drug combinations containing beta-benzalbutyrate. Clofibrate and its analogs (halofenate and beta-benzalbutyrate) produced significant hepat*****ly (mean responses of +18, +18 and +10%, respectively) whereas oxandrolone produced significant hepatic shrinkage (-10%)(P less than .05). Secondary effects (drug interactions) were also found; hypotriglyceridemic synergism (effects more than additive) occurred between oxandrolone and clofibrate or its analogs (P less than .05), whereas antagonism (effects less than additive) was observed within the clofibrate-like group (P less than .01 or less .05).
Volume 194, Issue 1, pp. 274-284, 07/01/1975
Copyright © 1975 by American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology And Experimental Therapeutics, Vol. 151, Issue 1, 143-150, 1966
Copyright © 1966 by American Society for Pharmacology and Experimental Therapeutics
RELATIVE EFFECTS OF 17agr-ALKYLATED ANABOLIC STEROIDS ON SULFOBROMOPHTHALEIN (BSP) RETENTION IN RABBITS
Harry D. Lennon 1
1 Endocrinology Department, Division of Biological Research, G. D. Searle and Company, Chicago, Illinois
Measurement of sulfobromophthalein (BSP) retention in rabbits was shown to be a simple laboratory test for estimating the effects of anabolic steroids on hepatic excretory function. Non-17agr-alkylated androgen-anabolic steroids failed to alter serum BSP levels, whereas 17agr-alkylated anabolic steroids caused increased BSP retention when these steroids were given orally to rabbits at 10 and 20 mg/kg of body weight daily for 4 days. The magnitude of effects on BSP retention in the rabbit varied among the various l7agr-alkylated steroids and did not appear to be related to myotrophic or androgenic activities, although some correlation was apparent with nitrogen-retaining activity in rats. Several published clinical reports indicated that the relative effects of 17agr-alkylated anabolic steroids on BSP retention in human patients were similar to those effects observed in rabbits.
Accepted on August 24, 1965
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Protective action of SCH 12223 against experimentally induced gastric and intestinal lesions
PJ Chiu, A Barnett, M Siegel, AD Brown and C Gerhart
Department of Pharmacology, Schering-Plough Corporation, Bloomfield, New Jersey.
The gastrointestinal protective action of SCH 12223 [3-(n-butyl)-4- hydroxy-1-phenyl-1,8-naphthyridin-2(1H)-one hydrate, sodium salt] against various noxious stimuli was characterized in rats. SCH 12223 inhibited the ethanol-induced gastric lesions when given p.o. (0.3-3 mg/kg) or i.v. (1 and 3 mg/kg). Indomethacin pretreatment (10 mg/kg p.o.) did not interfere with this effect. SCH 12223 was also active p.o. in five gastric erosion models: aspirin (1-10 mg/kg), aspirin + acid (1-30 mg/kg), indomethacin (1-10 mg/kg), stress (1 and 3 mg/kg) and reserpine (0.3-10 mg/kg)-induced erosions. The compound lacked antisecretory activity in the pylorus-ligated rats (10 mg/kg p.o.) but increased total gastric mucus (N-acetylneuraminic acid measurements) (1- 10 mg/kg p.o.). SCH 12223 (10 and 30 mg/kg p.o.) attenuated intestinal lesions provoked by indomethacin (20 mg/kg p.o. or s.c.) and the protected animals showed better weight gain and food intake than controls. In a 38-day study, SCH 12223 also improved survival from indomethacin lethality (6 of 16 vs. 16 of 16 in the control, P less than .05). The protection cannot be attributed to changes in biliary excretion and plasma levels of indomethacin. We conclude that SCH 12223 is a unique agent which protects both gastric and intestinal epithelia from noxious stimuli, a feature shared by prostaglandins.
Volume 246, Issue 2, pp. 578-584, 08/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology And Experimental Therapeutics, Vol. 153, Issue 2, 337-343, 1966
Copyright © 1966 by American Society for Pharmacology and Experimental Therapeutics
ANTICONVULSANT ACTIVITY OF STEROIDS: SEPARABILITY OF ANTICONVULSANT FROM HORMONAL EFFECTS
Charles R. Craig 1
1 Division of Biological Research, G. D. Searle & Co., Chicago, Illinois
In order to determine whether anticonvulsant effects and hormonal properties are intimately related among steroid compounds, the anticonvulsant activity of progesterone, desoxyconticosterone and other steroids was explored in mice. This activity was shown not to be a general characteristic of steroid compounds or to be closely associated with progestational or other hormonal effects. A series of 3beta-(aminoalkyl) esters of pregnenolone were examined for anticonvulsant activity, and the most active compound, 3beta-(3-N-pyrrolidinylpropionyloxy)-5-pnegnen-20-One (SC-10024), was additionally tested and was found to be devoid of hormonal effects. A brief clinical trial with SC-10024 showed it to exert beneficial effects in patients with epilepsy even though its activity was of such a low order that it precluded further testing.
Accepted on March 10, 1966