Systemic and regional hemodynamic and biological effects of a new kappa-opioid agonist, niravoline, in healthy volunteers
We noninvasively investigated the effects of a single 30-min i.v. infusion of a 2-mg dose of niravoline, a new selective kappa-opioid agonist, on systemic and regional (brachial artery) hemodynamics, on plasma levels of the main hormones regulating the cardiovascular system, on diuresis and on plasm...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 278; no. 1; pp. 232 - 242 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.07.1996
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Abstract | We noninvasively investigated the effects of a single 30-min i.v. infusion of a 2-mg dose of niravoline, a new selective kappa-opioid
agonist, on systemic and regional (brachial artery) hemodynamics, on plasma levels of the main hormones regulating the cardiovascular
system, on diuresis and on plasma and urinary osmolalities and electrolytes. This was a placebo-controlled, randomized, double-blind,
crossover study performed in 12 healthy volunteers. Compared with placebo, niravoline induced a significant, early and potent
diuresis, which peaked within 2 hr (urine output increased 2.4-fold) and lasted for 4 hr. Niravoline significantly decreased,
between 0 and 2 hr, urine osmolality (-71%) and sodium (-38%) and potassium (-29%) excretion and significantly increased plasma
osmolality and natremia, without changing kalemia. Niravoline induced a slight, but significant, increase in blood pressure
(+8% at 0.5 hr), which disappeared within 2 hr. Because heart rate, stroke volume and cardiac output were not modified, this
effect was due to an increase in total peripheral resistance (+22% at 0.5 hr). Niravoline did not modify brachial artery diameter
and flow and corresponding vascular resistance. Niravoline tended to decrease plasma vasopressin levels and urinary excretion
and significantly increased plasma levels of norepinephrine (+44% at 0.5 hr), active renin (+22% at 1.25 hr), aldosterone
(+52% at 1.25 hr) and atrial natriuretic factor (+20% at 2 hr). We conclude that niravoline induces a potent aquaretic effect
associated with antinatriuresis and antikaliuresis. These main effects are accompanied by a stimulation of the sympathetic
and reninangiotensin systems and a slight and transient increase in blood pressure. |
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AbstractList | We noninvasively investigated the effects of a single 30-min i.v. infusion of a 2-mg dose of niravoline, a new selective kappa-opioid agonist, on systemic and regional (brachial artery) hemodynamics, on plasma levels of the main hormones regulating the cardiovascular system, on diuresis and on plasma and urinary osmolalities and electrolytes. This was a placebo-controlled, randomized, double-blind, crossover study performed in 12 healthy volunteers. Compared with placebo, niravoline induced a significant, early and potent diuresis, which peaked within 2 hr (urine output increased 2.4-fold) and lasted for 4 hr. Niravoline significantly decreased, between 0 and 2 hr, urine osmolality (-71%) and sodium (-38%) and potassium (-29%) excretion and significantly increased plasma osmolality and natremia, without changing kalemia. Niravoline induced a slight, but significant, increase in blood pressure (+8% at 0.5 hr), which disappeared within 2 hr. Because heart rate, stroke volume and cardiac output were not modified, this effect was due to an increase in total peripheral resistance (+22% at 0.5 hr). Niravoline did not modify brachial artery diameter and flow and corresponding vascular resistance. Niravoline tended to decrease plasma vasopressin levels and urinary excretion and significantly increased plasma levels of norepinephrine (+44% at 0.5 hr), active renin (+22% at 1.25 hr), aldosterone (+52% at 1.25 hr) and atrial natriuretic factor (+20% at 2 hr). We conclude that niravoline induces a potent aquaretic effect associated with antinatriuresis and antikaliuresis. These main effects are accompanied by a stimulation of the sympathetic and reninangiotensin systems and a slight and transient increase in blood pressure. We noninvasively investigated the effects of a single 30-min i.v. infusion of a 2-mg dose of niravoline, a new selective kappa-opioid agonist, on systemic and regional (brachial artery) hemodynamics, on plasma levels of the main hormones regulating the cardiovascular system, on diuresis and on plasma and urinary osmolalities and electrolytes. This was a placebo-controlled, randomized, double-blind, crossover study performed in 12 healthy volunteers. Compared with placebo, niravoline induced a significant, early and potent diuresis, which peaked within 2 hr (urine output increased 2.4-fold) and lasted for 4 hr. Niravoline significantly decreased, between 0 and 2 hr, urine osmolality (-71%) and sodium (-38%) and potassium (-29%) excretion and significantly increased plasma osmolality and natremia, without changing kalemia. Niravoline induced a slight, but significant, increase in blood pressure (+8% at 0.5 hr), which disappeared within 2 hr. Because heart rate, stroke volume and cardiac output were not modified, this effect was due to an increase in total peripheral resistance (+22% at 0.5 hr). Niravoline did not modify brachial artery diameter and flow and corresponding vascular resistance. Niravoline tended to decrease plasma vasopressin levels and urinary excretion and significantly increased plasma levels of norepinephrine (+44% at 0.5 hr), active renin (+22% at 1.25 hr), aldosterone (+52% at 1.25 hr) and atrial natriuretic factor (+20% at 2 hr). We conclude that niravoline induces a potent aquaretic effect associated with antinatriuresis and antikaliuresis. These main effects are accompanied by a stimulation of the sympathetic and reninangiotensin systems and a slight and transient increase in blood pressure. |
Author | D G Bichet E Bellissant J F Giudicelli J M Gandon F Lecoz H Allain P Sinnassamy T Denolle |
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Snippet | We noninvasively investigated the effects of a single 30-min i.v. infusion of a 2-mg dose of niravoline, a new selective kappa-opioid
agonist, on systemic and... We noninvasively investigated the effects of a single 30-min i.v. infusion of a 2-mg dose of niravoline, a new selective kappa-opioid agonist, on systemic and... |
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SubjectTerms | Adult Atrial Natriuretic Factor - blood Benzeneacetamides Blood Pressure - drug effects Hemodynamics - drug effects Humans Kinetics Male Osmolar Concentration Pyrrolidines - pharmacology Receptors, Opioid, kappa - agonists Renin - blood |
Title | Systemic and regional hemodynamic and biological effects of a new kappa-opioid agonist, niravoline, in healthy volunteers |
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