Disease relevance of GO 687

• The low placental and fetal concentrations of etozolin and ozolinone suggest that these drugs may prove useful when a diuretic is indicated in the treatment of oedema and hypertension during pregnancy [1].
• Independent of etozolin elimination of kidney function. Single dose experiments in patients with renal insufficiency [2].
• Ascites concentrations of etozolin and ozolinone were almost identical to the plasma concentration [3].
• In cirrhosis, the plasma level time curves of etozolin and ozolinone differed significantly from the controls and also from those of the patients with acute hepatitis [3].
• The lack of correlation between elimination half-life (HL) and creatinine clearance showed that there is no influence of kidney disease on the pharmacokinetic parameters of etozolin and ozolinone [2].

High impact information on GO 687

• Determination of etozolin and ozolinone in human plasma and tissues by reversed-phase high-performance liquid chromatography [4].
• Pharmacodynamics and kinetics of etozolin/ozolinone in hypertensive patients with normal and impaired kidney function [5].
• The fetal tissue/maternal serum and placental tissue/maternal serum ratios of etozolin and ozolinone were found to lie between 0.3 and 0 [1].
• The ability of etozoline to reverse the noradrenaline-induced contraction was unaffected by pyrogallol, methylene blue or superoxide-dismutase [6].
• Acute antihypertensive, diuretic and metabolic effects of etozolin and chlorthalidone [7].

Chemical compound and disease context of GO 687

• A total of 1337 patients with mild to moderate essential hypertension were included in an open, multicentre trial to assess the response rate to the diuretic etozolin (200 mg once a day) and to verify whether the addition of the calcium antagonist verapamil (120 mg twice a day) in non-responders may have a favourable effect [8].

Biological context of GO 687

• Etozolin lowered diastolic blood pressure to below 95 mmHg in 67.8% of patients after 4 weeks of treatment and in 62.4% of patients after 12 weeks [8].
• Etozolin (50 mg/kg i.v. initial dose; 50 mg/kg per hour i.v.) markedly increased urinary fluid and sodium excretion and decreased glomerular filtration rate [9].
• In hepatitis, the elimination half-life of etozolin was 4 times longer resulting in a 2 fold rise in the AUC [3].
• 1. The distribution of radioactivity has been studied by whole-body autoradiography after administration of daily oral doses of (2-14C)-ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (etozolin, Gö 687, Elkapin) at a dose level of 100mg/kg to pregnant rats during the 10th to the 17th day of gestation [10].

Anatomical context of GO 687

• These results suggest that the vasodilating action of etozoline and of its metabolites is mediated by an inhibition of Ca++ influx into smooth muscle cells following a specific opening of K+ channels, but only etozoline may act through this mechanism at concentrations likely to be operative in vivo [11].
• The effects of ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (etozolin, Elkapin) on whole kidney function and on fluid, sodium and potassium reabsorption in proximal convoluted tubules and loops of Henle of superficial nephrons were studied in rats using clearance and micropuncture techniques [9].

Associations of GO 687 with other chemical compounds

• Tetraethylammonium, at concentrations reported to increase Ca++ influx into smooth muscle cells by closing K+ channels, induced contractions of aortic strips that were highly sensitive to inhibition by etozoline [11].
• Following a single oral dose of the novel diuretic ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (etozolin, Elkapin), the plasma levels of the parent drug and its active metabolite (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetic acid (ozolinone) were determined by means of HPLC [2].

Analytical, diagnostic and therapeutic context of GO 687

• Etozoline also inhibited contractions induced by increasing Ca++ concentrations in the perfusion medium of aortic strips depolarized by 40 mM K+ [11].

References