Effects of dilazep on coronary and systemic hemodynamics in humans

Marzilli, Mario; Simonetti, Ignazio; Levantesi, D; Trivella, Maria Giovanna; Nes, Michele De; Perissinotto, A.; Puntoni, Roberto; Buzzigoli, G.; Boni, Claudio De; Michelassi, Claudio; LʼAbbate, Antonio

doi:10.1016/0002-8703(84)90612-4

Cited by 17 publications

(2 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data support the recent findings o f Marzilli et al [25] who reported a sustained dilation o f human epicardial vessels when dilazep was administcred intravenously. It is quite likely that the clinical effects o f dilazep and lidoflazine are a combination o f their calcium entry-blocking effect on large vessels and adenosine uptake inhibition in resistance vessels [26],…”

Section: Discussionsupporting

confidence: 92%

Calcium Entry Blocking Activity of Dilazep in Dog Coronary Artery

Nakagawa

Gudenzi

1986

Pharmacology

View full text Add to dashboard Cite

Calcium entry blocking activities of adenosine and its potentiating compounds (dipyridamole, lidoflazine and dilazep) were studied in potassium (100 mmol/l) depolarized, dog, large coronary artery strips, in comparison to nifedipine, verapamil and diltiazem. Apparent pA₂ values were calculated by using concentration-response curves for calcium before and 30 min after the addition of each dilator drug. The order of potency (using both pA₂ and IC₅₀ values) for the calcium entry blocking effect was: nifedipine > verapamil > diltiazem > lidoflazine > dilazep. Dipyridamole and adenosine had negligible calcium entry blocking activities (about 10,000 times less potent than verapamil). The calcium entry blocking activity of verapamil (using pA₂ values) was 39.8 times less potent than nifedipine, and 3.6, 21.4 and 97.7 times more potent than diltiazem, lidoflazine and dilazep, respectively. The maximum relaxations induced by adenosine (3.7 × 10^–4 mol/l) and dipyridamole (5 × 10–⁵ mol/l) were less than 20% that of 3 × 10^–4 mol/l papaverine. However, the other test drugs caused 80–90% relaxation under similar conditions. The relaxing effect of adenosine was inhibited by 8-phenyltheophylline (adenosine receptor antagonist) and potentiated by EHNA (an adenosine deaminase inhibitor), while dilazep-induced relaxation was not affected by these drugs. These findings suggest that the calcium entry blocking effect of dilazep in dog, large coronary artery strips is not mediated through adenosine.

show abstract

Section: Discussionsupporting

confidence: 92%

Calcium Entry Blocking Activity of Dilazep in Dog Coronary Artery

Nakagawa

Gudenzi

1986

Pharmacology

View full text Add to dashboard Cite

show abstract

“…In fact, the cardioprotective (or anti-ischemic) effect of dilazep was reported in the dog heart (2)(3)(4). In clinical studies, dilazep has been used successfully as a drug for treatment of patients with ischemic heart disease (5,6). However, the coronary vasodilating action of dilazep is not very marked, suggesting that there is another mechanism for the anti-ischemic action of dilazep.…”

mentioning

confidence: 99%

A Study on Dilazep: I. Mechanism of Anti-ischemic Action of Dilazep Is Not Coronary Vasodilation but Decreased Cardiac Mechanical Function in the Isolated, Working Rat Heart

Hoque

Hashizume

et al. 1995

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-In the isolated, perfused working rat heart, ischemia (15 min) decreased the mechanical function and the tissue levels of adenosine triphosphate and creatine phosphate and increased the levels of lactate and free fatty acids. Reperfusion (20 min) did not restore the mechanical function, but restored incompletely the levels of metabolites, with the exception of free fatty acids, which increased further during reperfusion. Dilazep was given 5 min before starting ischemia until the end of ischemia. Dilazep at 5 or 10 pM decreased the cardiac mechanical function, but did not affect coronary flow in the pre-ischemic heart. Dilazep at 5 or 10 pM accelerated the recovery of mechanical function and coronary flow during reperfusion, and it attenuated metabolic changes induced by ischemia and reperfusion. Dilazep at 1 pM neither decreased the pre-ischemic mechanical function nor restored the mechanical function during reperfusion, although it attenuated the accumulation of free fatty acids during reperfusion. These results suggest that dilazep attenuates both ischemia-and reperfusion-induced myocardial damage and that the anti-ischemic action of dilazep is not due to coronary vasodilation but probably due to an energy-sparing effect and other effects that remain to be studied.

show abstract

Intravenous Dilazep Reduces Blood Pressure and Peripheral Vascular Resistance in Humans

Poggesi

Masotti

Serneri

1988

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Dilazep, a coronary vasodilating drug with adenosine-mediated activity, was tested (acute double-blind study versus placebo) for its antihypertensive activity in 12 patients who had mild to moderate hypertension. Dilazep (0.2 mg/kg body weight by IV infusion for ten minutes) significantly reduced systolic and diastolic blood pressure (random-zero sphygmomanometer) on average by 13.3 and 10.6 mm Hg respectively. The antihypertensive effect started rapidly, reached its maximum 20 minutes after administration, and lasted for 90 minutes. Heart rate significantly increased between 10 and 30 minutes. The antihypertensive effect of dilazep was associated with a relevant vasodilating effect as demonstrated by the changes in upper limb blood flow (strain-gauge plethysmography, +32%; P less than .001) and vascular resistance (-29%, P less than .001). The maximal reduction of vascular resistance was directly correlated to its baseline value. For these characteristics of action, at least in acute administration, dilazep would be useful agent for the treatment of high blood pressure in mild to moderately hypertensive patients.

show abstract

Effects of dilazep on coronary and systemic hemodynamics in humans

Cited by 17 publications

References 19 publications

Calcium Entry Blocking Activity of Dilazep in Dog Coronary Artery

Calcium Entry Blocking Activity of Dilazep in Dog Coronary Artery

A Study on Dilazep: I. Mechanism of Anti-ischemic Action of Dilazep Is Not Coronary Vasodilation but Decreased Cardiac Mechanical Function in the Isolated, Working Rat Heart

Intravenous Dilazep Reduces Blood Pressure and Peripheral Vascular Resistance in Humans

Contact Info

Product

Resources

About