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Acta Neuropathologica Oct 1978The present study presents evidence for a third hypocholesterolemic drug, zuclomiphene, being able to induce an experimental myotonic condition. Other drugs used singly...
The present study presents evidence for a third hypocholesterolemic drug, zuclomiphene, being able to induce an experimental myotonic condition. Other drugs used singly or in combination were AY-9944, Triparanol and 20, 25-diazacholesterol. It has also been demonstrated for the first time that experimental myotonia can be induced in developing rats as well as adults. Developing rats received the initial intraperitoneal injections of drug at 5 days of age and were examined at 50 days of age. Adult rats were treated for 5 weeks. Two injections were given per week. Positive electromyography findings were observed in the developing and adult animals receiving 20, 25-diazacholesterol and zuclomiphene. The electromyography data of the other regimens of treatment were equivocal with regard to myotonia. Histological, histochemical, and electron microscopic examination of the muscle demonstrated no important changes. estimation of sterol composition showed that desmosterol was a major sterol in muscle after 20, 25-diazacholesterol or zuclomiphene treatment, thus furthering the concept that it is desmosterol in the muscle membrane, and not the drug, that is responsible for the myotonic condition.
Topics: Animals; Anticholesteremic Agents; Azacosterol; Electromyography; Female; Male; Muscles; Myotonia; Rats; trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride
PubMed: 81585
DOI: 10.1007/BF00691634 -
The Journal of Pharmacology and... Aug 1982
Topics: Action Potentials; Animals; Azacosterol; Cholesterol; Male; Membrane Potentials; Muscle Contraction; Muscles; Myotonia; Ouabain; Potassium; Rats; Rats, Inbred Strains; Sodium; Tetrodotoxin
PubMed: 7097560
DOI: No ID Found -
International Journal of Fertility 1987The effects of 22,25-diazacholesterol dihydrochloride (SC-12937) on the spermatogenesis of the bandicoot rat (Bandicota bengalenesis), heretofore unreported on any...
The effects of 22,25-diazacholesterol dihydrochloride (SC-12937) on the spermatogenesis of the bandicoot rat (Bandicota bengalenesis), heretofore unreported on any mammalian species, were studied. Rats were given a single subcutaneous injection of SC-12937 at a dosage of 100 or 200 mg/kg body weight and were killed on days 2 or 10 post-injection. Quantitative analysis of the germinal epithelium was performed on testicular sections (5 micron) stained with periodic acid-Schiff-hematoxylin to assess spermatogenesis. Treatment with SC-12937 at both dosages was found to interfere with the spermatogenic process of this pest rat. In addition to its antispermatogenic action, at higher dosage (200 mg/kg), this compound produced a marked suppression in accessory organ function. The results indicate that a single administration of SC-12937 in low dosage can cause spermatogenic inhibition without affecting accessory organ function in the bandicoot rat.
Topics: Animals; Azacosterol; Cholesterol; Male; Muridae; Spermatogenesis; Spermatogenesis-Blocking Agents
PubMed: 2887533
DOI: No ID Found -
Journal of Reproduction and Fertility Mar 1981The spontaneous ovulation of hens was suppressed by daily injection of PMSG. The LH injected to overcome the block was accompanied by one of 4 compounds known to inhibit...
The spontaneous ovulation of hens was suppressed by daily injection of PMSG. The LH injected to overcome the block was accompanied by one of 4 compounds known to inhibit steroidogenesis at different sites in the biosynthetic pathway. A dose of 300 mg aminoglutethimide phosphate, which inhibits the conversion of cholesterol to 20 alpha-hydroxycholesterol, blocked the LH-induced ovulation and prevented the normal rise in plasma progesterone. Metyrapone, an inhibitor of 11 beta-hydroxylase, and SC 12937 and AY 9944, inhibitors of cholesterol synthesis, did not prevent ovulation or the progesterone rise induced by exogenous LH. Administration of progesterone overcame the inhibitory effect of aminoglutethimide, and it is suggested that progesterone is involved in the ovulatory process of the fowl.
Topics: Aminoglutethimide; Animals; Azacosterol; Chickens; Female; Gonadotropins, Equine; Luteinizing Hormone; Metyrapone; Ovulation; Ovulation Induction; Progesterone; trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride
PubMed: 6162953
DOI: 10.1530/jrf.0.0610381 -
Biochemical and Biophysical Research... Jun 1979
Topics: Animals; Azacosterol; Cell Survival; Cells, Cultured; Chick Embryo; Cholesterol; Chromatography, Gas; Desmosterol; Mass Spectrometry; Muscles; Steroids
PubMed: 572680
DOI: 10.1016/0006-291x(79)91522-5 -
Experimental Neurology Jun 1982
Topics: Animals; Azacosterol; Biomechanical Phenomena; Cholesterol; Electric Conductivity; Male; Motor Endplate; Neuromuscular Junction; Rats; Rats, Inbred Strains
PubMed: 7084383
DOI: 10.1016/0014-4886(82)90136-4 -
European Journal of Pharmacology Apr 1993It has been reported that an enantiomer ((S)-(-)-4) of clofibric acid, and the racemate, can block the chloride conductance of skeletal muscle membrane. It has also been...
It has been reported that an enantiomer ((S)-(-)-4) of clofibric acid, and the racemate, can block the chloride conductance of skeletal muscle membrane. It has also been reported that several analogs of clofibric acid inhibit the HCO3(-)-Cl- exchange of erythrocytes. Since the two effects are probably similar biophysical membrane phenomena, the possibility of a common molecular mechanism arises. We exposed Sprague-Dawley male rats to long-term administration of clofibrate and 20,25-diazacholesterol (20,25-D) for comparison, at equipotent doses. Clofibrate (but not 20,25-diazacholesterol) produced a significant increase in density of the 220,000 Da band (beta-spectrin) and a decrease, also significant, in density of bands 2.1, 2.2, 2.3, 2.6 (syndeins or ankyrins) and of bands 4.1 and 6. Thus, clofibrate exhibits a manifold effect on the protein profile of the erythrocyte membrane cytoskeleton which, due to the lack of effect of 20-25-D, does not seem to be produced by the hypolipidemic effect per se, and thus deserves further study.
Topics: Animals; Azacosterol; Blood Proteins; Cholesterol; Clofibrate; Cytoskeleton; Densitometry; Erythrocyte Membrane; Indicators and Reagents; Male; Microscopy, Electron, Scanning; Osmotic Fragility; Rats; Rats, Sprague-Dawley
PubMed: 8491258
DOI: 10.1016/0922-4106(93)90115-p -
Experimental Neurology Feb 1982
Topics: Action Potentials; Animals; Azacosterol; Biomechanical Phenomena; Disease Susceptibility; Leg; Male; Membrane Potentials; Muscles; Myotonia; Nerve Regeneration; Rats; Rats, Inbred Strains
PubMed: 7106224
DOI: 10.1016/0014-4886(82)90174-1 -
Biomedical Mass Spectrometry Jul 1982Radiogas chromatography, used in conjunction with mass spectrometry, has been used to analyze the sterol content of cultured chick muscle cells. Seven sterols, plus...
Effects of 20,25-diazacholesterol on cholesterol synthesis in cultured chick muscle cells: a radiogas chromatographic and mass spectrometric study of the post-squalene sector.
Radiogas chromatography, used in conjunction with mass spectrometry, has been used to analyze the sterol content of cultured chick muscle cells. Seven sterols, plus lanosterol, were detected. These sterols conformed to a linear biosynthetic pathway linking lanosterol and cholesterol. The reaction sequence is: C-14 demethylation, C-4 demethylation, delta 8 leads to delta 5 double bond rearrangement, delta 24 double bond reduction. When chick cells were treated with increasing concentrations of 20,25-diazacholesterol, components of this pathway and aberrant products accumulated. These accumulations suggest that diazacholesterol affects reductases, double bond isomerases and the C-14 demethylation enzymes of sterol biosynthesis.
Topics: Animals; Azacosterol; Cells, Cultured; Chick Embryo; Cholesterol; Desmosterol; Gas Chromatography-Mass Spectrometry; Lanosterol; Muscles; Squalene
PubMed: 7126761
DOI: 10.1002/bms.1200090703 -
Biochemical and Biophysical Research... Sep 1980
20,25-Diazacholesterol, clofibric acid and 2,4-dichlorophenoxyacetic acid--all inducers of myotonia--perturb the post-lanosterol sector of sterol biosynthesis in cultured chick embryo fibroblasts.
Topics: 2,4-Dichlorophenoxyacetic Acid; Acetates; Animals; Azacosterol; Cells, Cultured; Chick Embryo; Cholesterol; Chromatography, Gas; Clofibrate; Clofibric Acid; Fibroblasts; Lanosterol; Muscles; Sterols
PubMed: 7437038
DOI: 10.1016/0006-291x(80)91177-8