Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Cadralazine is a new antihypertensive agent which causes peripheral vasodilation, probably mediated by a hydrazinopyridazine metabolite. 2. The possible influence of acetylator status on the pharmacokinetics and haemodynamics of the drug was studied in six fast and six slow acetylators over a period of 24 h after administration of a single 10 mg oral dose. 3. There were no differences between the two groups in AUC and Cmax values of cadralazine and apparent metabolite, the latter defined as the sum of the free and conjugated hydrazinopyridazine. Peak plasma concentrations of these compounds were reached after 1 h. Thereafter, the concentration of the metabolite declined more slowly than that of cadralazine. 4. No effects on blood pressure were noted. Changes in heart rate and plasma renin were delayed by 3-5 h with respect to the time-course of drug and metabolite in plasma; maximum responses occurred at 4-6 h after drug administration. The extent of the increase in plasma renin activity was slightly greater in slow than in fast acetylators, but the difference was not significant statistically.
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PMID:Influence of acetylator status on the haemodynamic effects and pharmacokinetics of cadralazine in healthy subjects. 219 Jun 29

Cadralazine is a new antihypertensive drug, acting as a peripheral arteriolar vasodilator through its hydrazinopyridazine metabolite. Since this metabolite actively contributes to the activity of the drug, we administered in a double blind randomized study 10 mg/placebo o.d. to 6 healthy fast and 6 slow normotensive acetylators in order to investigate the influence of the acetylator status on hemodynamics and pharmacokinetics. Blood pressure was measured with a DINAMAP apparatus, forearm hemodynamics with a pulsed doppler and central hemodynamics with impedance-cardiography; active renin (RIA), cadralazine and its metabolite (HPLC) were measured during the 11 measurement points. The results were analysed with repeated analysis of variance (ANOVA). Heart rate significantly increased (p less than 0.001), until the 24th hour (p less than 0.05), meanwhile blood pressure and forearm hemodynamics did not change. Cardiac output was increased as a consequence of the elevation in venous return. The rise in active renin paralleled the increase in heart rate with a significant correlation (r' = 0.580, p less than 0.05). The magnitude of the increase was higher in slow than that in fast acetylators, but did no reached the significance. No differences were found for AUC, Cmax and Tmax between the two groups but the active metabolite was eliminated slower than that of cadralazine. The time course of the effects on heart rate and plasma renin was not parallel to the plasma levels of cadralazine and its metabolite. With respect to the power of the study (1-beta = 80 p. 100), no significant differences were found between the two groups.
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PMID:[Influence of acetylation phenotype on the pharmacokinetics and pharmacodynamics data of cadralazine in normotensive subjects]. 251 Jun 57

The effect of the antihypertensive vasodilator, cadralazine, on renal function in the conscious dog was compared to that of hydralazine using inulin and para-aminohippurate clearances. Both drugs were administered as intravenous bolus, at the dose of 1 mg/kg. As expected, hydralazine rapidly decreased mean blood pressure (from 110 to 89 mmHg), significantly increased heart rate (from 109 to 190 beats/min), markedly decreased urine volume (from 0.90 to 0.47 ml/min) and sodium excretion (from 101 to 45 microEq/min), and increased potassium excretion (from 28 to 53 microEq/min). Cadralazine displayed a similar activity on blood pressure and on heart rate, but differently from hydralazine, these effects appeared more slowly and were not accompanied by sodium and water retention. Hydralazine, but not cadralazine, caused a quick and transient decrease in glomerular filtration rate (from 55 to 40 ml/min), whereas both compounds increased renal plasma flow and reduced renal vascular resistance, renal extraction of para-aminohippurate and filtration fraction. Moreover, cadralazine increased plasma renin activity to a lesser extent than hydralazine, and this could explain the different effect on water and sodium excretion after acute administration of the two drugs.
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PMID:Renal function studies with cadralazine in conscious dogs: a comparison with hydralazine. 266 51

The antihypertensive effects of the hydralazine-related compound cadralazine (2-(3-[6-(2-hydroxypropyl)ethylamino]pyridazinyl)ethyl carbazate, ISF 2469), were investigated in 16 patients with primary hypertension concurrently treated with beta-blockers and diuretics. The protocol included a double-blind placebo controlled haemodynamic evaluation after the first tablet and two 4-week double-blind placebo controlled cross-over periods followed by an open evaluation during 2 months. Cadralazine induced a moderate, prolonged fall in blood pressure that was associated with vasodilatation and slight increases in cardiac output (dye-dilution) and heart rate. Renal plasma flow (PAH) and glomerular filtration rate (51Cr-EDTA) were not significantly influenced, but the filtration fraction was reduced. Plasma concentrations of noradrenaline and adrenaline rose, whereas plasma renin activity was unchanged. The haemodynamic parameters were not correlated with the plasma concentrations of cadralazine. During chronic cadralazine treatment the supine blood pressure was significantly lower than during the double-blind placebo phase (160/93 vs 174/102 mmHg). The compound was generally well tolerated but the body weight increased slightly (1.1 kg), probably because of fluid retention. Several patients who had previously experienced side effects with hydralazine, including one with hydralazine-syndrome, tolerated cadralazine well. This suggests that cadralazine does not cross-react with hydralazine.
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PMID:Acute systemic and renal haemodynamic effects and long-term antihypertensive action of cadralazine in patients pretreated with beta-blockers and diuretics. 288 88