piperidines and ozolinone

The effects of the diuretic drug ozolinone on electrogenic Cl- secretion by rabbit colonic mucosa were investigated in vitro. Electrical properties and unidirectional Cl- fluxes were measured in stripped preparations mounted in Ussing-type chambers. After abolition of electrogenic Na+ absorption by amiloride (10(-4) mol/l) on the mucosal side electrogenic Cl- secretion was induced by addition of PGE1 (10(-6) mol/l, serosal side) and theophylline (10(-2) mol/l, both sides). Under these conditions, the monitored short-circuit current (Isc) equals the amount of Cl- secreted as evidenced by determination of unidirectional Cl- fluxes. After establishing a stable Cl- secretion its sensitivity to the enantiomers of the diuretic was studied. Only levorotatory (-)-ozolinone, but not the dextrorotatory (+)form, inhibited Cl- secretion on serosal application. This effect was fully accounted for by a reduction in the serosal-to-mucosal Cl- fluxes (JClsm). It was readily reversible and concentration-dependent with a Ki value of 6 x 10(-4) mol/l, but absent when the drug was added to the mucosal side. The results are in agreement with the hypothesis that loop diuretics inhibit a coupled NaCl entry mechanism across the baso-lateral membrane into colonic epithelial cells. This mechanism is though to account for Cl- influx into the cells.

Topics: Animals; Chlorides; Colon; Diuretics; Female; In Vitro Techniques; Male; Piperidines; Rabbits; Stereoisomerism; Thiazoles

Topics: Adenosine Triphosphatases; Amidines; Animals; Biological Transport, Active; Cell Membrane Permeability; Chlorides; Diuretics; Furosemide; Kidney Tubules; Loop of Henle; Muzolimine; Ouabain; Oxygen Consumption; Piperidines; Rabbits; Sodium; Sodium-Potassium-Exchanging ATPase; Thiazoles

Topics: Animals; Diuretics; Dose-Response Relationship, Drug; Ear, Inner; Endolymphatic Sac; Ethacrynic Acid; Guinea Pigs; Microelectrodes; Piperidines; Potassium; Stria Vascularis; Thiazoles

Topics: Action Potentials; Animals; Bumetanide; Cats; Cochlea; Diuretics; Dose-Response Relationship, Drug; Female; Furosemide; Hearing Disorders; Male; Perfusion; Piperidines; Sulfonamides; Thiazoles; Vestibulocochlear Nerve

Topics: Chromatography, High Pressure Liquid; Female; Fetus; Humans; Maternal-Fetal Exchange; Piperidines; Placenta; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Reference Values; Thiazoles

The renal actions of the optically active isomers of the new diuretic drug ozolinone were studied by clearance, flowmeter and micropuncture techniques in rats. The levorotatory, but not the dextrorotatory isomer of ozolinone increased urine flow, urinary sodium and chloride excretion and enhanced sodium and chloride concentrations in early distal tubular fluid as checked by in situ microperfusion of Henle's loops. This indicates stereospecificity of the drug's diuretic action. However, both isomers of ozolinone equally inhibited maximal tubular secretion of paraaminohippurate and increased renal blood flow as measured by an electromagnetic flowmeter. Thus, the different renal target structures of ozolinone differ markedly with respect to stereoselectivity.

Topics: Animals; Chlorides; Diuretics; Glomerular Filtration Rate; Kidney; Kidney Tubules, Distal; Loop of Henle; Male; p-Aminohippuric Acid; Piperidines; Rats; Regional Blood Flow; Sodium; Thiazoles

The effect of the non-diuretic dextrorotatory isomer of ozolinone on furosemide-induced diuresis was studied by means of clearance and micropuncture techniques in rats. After intravenous injection, d-ozolinone antagonized the furosemide-induced increase in renal fluid and electrolyte excretion in a dose-related manner. Microperfusion experiments of Henle's loop in vivo revealed that d-ozolinone did not interfere with the action of furosemide at this tubular site. However, d-ozolinone markedly decreased the furosemide to inulin clearance ratio, presumably as a consequence of inhibition of furosemide secretion into the proximal tubules. It is assumed that, in consequence of a high affinity for the proximal organic acid transport system, d-ozolinone depresses proximal tubular furosemide secretion and prevents transfer of this diuretic to the tubular fluid. Thus, under the influence of d-ozolinone, furosemide cannot reach the loop of Henle in sufficient amounts and its diuretic effect is blocked.

Topics: Animals; Diuresis; Diuretics; Furosemide; Glomerular Filtration Rate; Kidney; Kidney Tubules, Proximal; Loop of Henle; Male; Piperidines; Rats; Regional Blood Flow; Thiazoles

A sensitive and specific method for the determination of the diuretic Ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (etozolin, Elkapin) and its pharmacologically active main metabolite, (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetic acid (ozolinone), at therapeutic concentrations in plasma is described. The method is based on high performance liquid chromatography and the use of two structurally similar internal standards. Etozolin and its metabolite are extracted from the plasma into dichloromethane at pH 9 and pH 5, respectively, and the resulting residues are analyzed on a silica gel column. The elution peaks are detected by UV absorption at 281 nm. The sensitivity for both compounds is 20 ng/ml plasma. The precision of the method is about +/- 5%. The applicability to pharmacokinetic studies of etozolin is shown.

Topics: Benzothiadiazines; Chromatography, High Pressure Liquid; Diuretics; Humans; Piperidines; Sodium Chloride Symporter Inhibitors; Thiazoles; Time Factors