The effective plasma concentrations of sulmazol (AR‐L 115 BS) on haemodynamics in chronic heart failure.

Renard, Marc; Jacobs, Paul; Mols, Pierre; Mélot, Christian; Dresse, A; Bernard, Roland

doi:10.1111/j.1365-2125.1983.tb02167.x

Cited by 2 publications

(1 citation statement)

References 12 publications

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“…The imidazo [4,5b] pyridine, sulmazole (AR-L 11 5BS), in man (Thormann et al, 1982;Renard et al, 1983). in vitro has been found to enhance the contractility of These effects in vivo are also accompanied by evidence isolated heart muscle (Dahmen & Greef, 1981; of vasodilator activity.…”

Section: Introductionmentioning

confidence: 99%

A comparative study of the cardiovascular and biochemical actions of the imidazo [4,5b] pyridine sulmazole and an imidazo [4,5c] pyridine analogue, BW A746C

Allan

Cambridge

Follenfant

et al. 1988

British J Pharmacology

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A comparative study of the cardiovascular and biochemical actions of the imidazo [4,5b] pyridine sulmazole and an imidazo [4,5c] 2 In anaesthetized guinea-pigs, dogs and primates, a bolus i.v. injection of BWA746C, (0.001-1.0 mg kg-') caused a significant, dose-related increase in ventricular dP/dt, and reduction in diastolic blood pressure, with small increases in heart rate. In these species, a significantly higher dose of BW A746C was required to lower blood pressure by 30% from basal, than was needed to raise ventricular dP/dt by 50% over basal.3 In anaesthetized guinea-pigs and dogs, bolus i.v. injections of sulmazole (0.1-10.0mg kg-')caused similar effects to those observed with BW A746C. In these species, however, there was no significant difference between the dose of sulmazole required to lower blood pressure by 30% from basal and that required to raise ventricular dP/dt by 50%. 4 In conscious dogs, i.v. infusion of BW A746C (to a total dose of 0.3 mg kg-') caused a significant increase in ventricular dP/dt, but no significant change in either diastolic blood pressure or heart rate. 5 In cell-free biochemical assays, there were no clear differences between the observed activities of BW A746C and sulmazole. Both compounds are cyclic nucleotide phosphodiesterase inhibitors with similar potencies and selectivities for the Type III enzyme (IC-, BW A746C = 3.0 ± 0.5 x 10-'M, sulmazole 5.0 ± 1.9 x 10-' M). The compounds had little or no effects on sarcolemmal Na+/ K+-ATPase, Ca"+ ATPase or Na+/Ca2" exchange, and sulmazole, but not BW A746C, had a small, stimulatory effect on myofibrillar ATPase.6 In anaesthetized guinea-pigs and dogs, BW A746C was significantly more potent as a positive inotrope than sulmazole. In contrast with sulmazole, BW A746C produced its inotropic effects at significantly lower doses than those required to reduce diastolic blood pressure. This was also apparent from the results obtained in the anaesthetised primates and the conscious dogs. It was therefore concluded that the inotropic/vasodilator profile of BW A746C favours its positive inotrope activity.This profile cannot be explained on the basis of any biochemical differences from sulmazole.

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Section: Introductionmentioning

confidence: 99%