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R M Stote

Publications and source records attributed to R M Stote.

27 records · Page 2Linked to original sources
PubMed1979

Studies with a PNMT inhibitor.

DCTQ (SK&F 64139) is a potent inhibitor of both adrenal and central nervous system (CNS) phenylethanolamine N-methyltransferase (PNMT). In animal studies, a plasma level of 0.35 microgram/ml was associated with 50% inhibition of both adrenal and central PNMT. We performed single-dose phase I studies with DCTQ in man. Plasma drug levels up to 6.26 microgram/ml were readily obtained. There were few subjective and no objective clinical changes. DCTQ did not alter blood pressure or cause CNS symptoms in man. Furthermore, resting plasma and urinary catecholamines did not change after DCTQ. The study suggests that acute inhibition of PNMT under resting conditions is without significant clinical effect.

Adrenal Glands↗
PubMed1979

Ticrynafen: site of natriuretic activity.

Studies were performed with ticrynafen (tienilic acid) to determine its natriuretic site of action, detailed electrolyte excretion, and its effect on acid excretion and bicarbonate reabsorption. With 500 and 1,000 mg oral doses under conditions of water diuresis, there was a decrease in free water excretion as osmolar clearance increased. During hydropenia, there was no change in free-water reabsorption as osmolar clearance increased. Maximum sodium excretion reached 5.2% of the filtered load. At 500 mg doses, there was no effect on phosphate excretion; with 1,000 mg doses, there was a reduction in phosphate excretion. During bicarbonate infusion, there was no change in the absolute or percent reabsorption of bicarbonate. After chronic administration of ticrynafen, there was no impairment of excretion of al acute acid load. Uric acid excretion increased at least threefold in all studies. The studies indicate that at 500 and 1,000 mg oral doses, ticrynafen has the characteristics of a diuretic which is active in the cortical diluting segment of the distal nephron.

Adult↗
PubMed1979

Tienilic acid: pharmacokinetics, salicylate interaction and creatinine secretion studies.

Tienilic acid is a diuretic-uricosuric compound whose natriuretic site of action is in the cortical diluting segment of the distal nephron. Oral doses of 250 mg given to normal human volunteers provided peak blood levels of 10--11 micrograms/ml at 3--4 hours after administration. Approximately 40% of the dose was recovered in 24 hours, 30% as the parent compound and 10% as the alcohol and diacid metabolites. A 650 mg dose of acetylsalicylic acid significantly decreased the uricosuric effect of tienilic acid by inhibiting uric acid secretion. Urine pH fell significantly with tienilic acid administration. Tienilic acid inhibited salicylate excretion by either competition for tubular secretion or by increasing passive, pH dependent reabsorption. In normal subjects given a creatinine load, tienilic acid did not inhibit creatinine secretion.

Adult↗
PubMed1978

Ticrynafen, a uricosuric antihypertensive diuretic.

Ticrynafen, a diuretic-uricosuric also effective as an antihypertensive, was compared in single doses with several other diuretics. Over an 8-hr period, a 250- mg dose exerted natriuretic activity comparable to that of 25 mg of chlorthalidone and 50 mg of ethacrynic acid; a 500-mg dose was comparable to 50 mg chlorthalidone and 50 mg hydrochlorothiazide. Ticrynafen combined with furosemide had an additive effect, whereas a combination with hydrochlorothiazide was not additive. In both doses ticrynafen was a uricosuric and this effect was maintained when given with furosemide and hydrochlorothiazide, both of which individually were slightly antiuricosuric. Ticrynafen may be useful in patients requiring a diuretic in whom it is desirable to avoid hyperuricemia.

Adult↗
PubMed1978

Effect of cimetidine on renal function in normal man.

To evaluate the effect of acute histamine H2-receptor blockade on renal function, renal function studies were performed in a control state and after cimetidine. Studies included acid excretion in response to acid loading, bicarbonate reabsorption during bicarbonate infusion, and urinary concentrating ability. Cimetidine produced no significant effect on any of these functions. During bicarbonate infusion, inulin clearance remained constant while creatinine clearance fell, possibly because of an effect on tubular creatinine secretion.

Adult↗
PubMed1978

Bioavailability of cimetidine in man.

The bioavailability of parenteral cimetidine was tested in 12 volunteers in a balanced three-way crossover study. Blood levels and urinary excretion were compared after intramuscular and intravenous injection and oral administration of 300 mg of cinetidine. The results indicated that the intramuscular and intravenous routes are virtually interchangeable for parenteral cimetidine, and that the oral liquid, although exhibiting a reduced area under the blood level curve as compared with the parenteral doses, nevertheless demonstrated equivalence with respect to the time the blood level remained above 0.5 microgram per ml. The 300-mg cimetidine tablet formulation was found in another group of 12 volunteers to be bioequivalent to a 300-mg dose of oral liquid.

Administration, Oral↗
PubMed1975

Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion.

We have studied the effects of demeclocycline on the water metabolism of a patient with the syndrome of inappropriate antidiuretic hormone (ADH) secretion who presented with a serum sodium concentration of 110 meq/litre. Free water clearance was studied before, during, and after treatment with demeclocycline. This study shows that demeclocycline (900 mg/day) can at least partially inhibit the action of ADH in the setting of tumor-induced ADH secretion, with the production of a reversible, partial nephrogenic diabetes insipidus, and with few or no side effects. Demeclocycline may be useful in the treatment of chronic inappropriate ADH secretion.

Carcinoma, Small Cell↗