Sacubitril/Valsartan Sodium Hydrate
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2015
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AT1;
NEP
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Recombinant protein, NEP and NEP-2 enzyme activity assay.
Rat cardiac fibroblasts, anti-fibrotic effects.
Rat cardiomyocytes, anti-hypertrophic effect.
Rat and human renal cortex tissue, NEP activity.
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Conscious rats, effect on ANP potentiation; evaluation of changes of
markers both the RAAS and the NP system; Bradykinin action.
Conscious dogs, effect on ANP potentiation; evaluation of changes of
markers of both the RAAS and the NP system; cGMP.
SHRSP, effect on vascular remodeling and cardiac fibrosis, cardiac
arteriole size, collagen deposltion, and MMP-2 activity.
Dahl Salt-Sensitive rat, effect on left-ventricular weight; diuresis
and natriuresis; blood pressure; renal function; urinary cGMP.
MI rat models, Cardiac remodeling.
Double-transgenic rat, effect on blood pressure.
DOCA rat, effect on blood pressure.
SHR, effect on blood pressure.
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FDA reviews: 207620Orig1s000
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Macitentan
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2013
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Tissue-targeting dual endothelin receptor
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ETA and ETB, receptors stably expressed CHO cell, binding assays;
effect on intracellular calcium.
Isolated rat aorta and trachea, inhibition of ET-1- induced
contraction in isolated tissues.
Pulmonary arterial smooth muscle cells, inhibitory potency and
dissociation kinetics.
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Normal rats, ET-1 plasma concentrations; Hemodynamic effects.
Guinea pigs, effects on electrocardiogram intervals.
Conscious dogs, electrocardiogram intervals and arterial blood
pressure.
Dahl salt-sensitive rats, effects on mean arterial blood pressure and
heart rate.
Deoxycorticosterone acetate (DOCA)-salt rats, effects on blood
pressure and heart rate.
Monocrotaline induced pulmonary hypertension in conscious wistar rats,
effect on mean pulmonary arterial pressure; and on the development of
pulmonary arterial wall thickness, right ventricular hypertrophy and
survival.
Rat model of bleomycin-induced pulmonary hypertension and fibrosis,
effect on right ventricular hypertrophy.
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FDA reviews: 204410Orig1s000
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Tolvaptan
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2009
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V2R
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Human endocervical carcinoma cell line (Hela cells) expressing human
AVP receptor subtypes, antagonistic effects.
Hela cells expressing human AVP V2-receptor, antagonistic effects.
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Water-loaded, alcohol-anesthetized rats, evaluation of the inhibitory
effect of V2-receptor antagonist tolvaptan on AVP-induced
antidiuresis.
Health animals
Aquaretic effect of orally administered tolvaptan was investigated in
conscious B6C3F1 mice, SD rats, and New Zealand white rabbits. Tolvaptan
increased urine volume and decreased urine osmolality.
Aquaretic effect of tolvaptan was examined on serum AVP, pituitary AVP
and the number of AVP receptors in the liver and in the kidney in male
SD rats.
Animal model of HF
Conscious, pacing-induced HF model of dogs, aquaretic effect.
Rat acute and chronic models of hyponatremia, effects on hyponatremia.
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FDA reviews: NDA 22-275
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Ivabradine Hydrochloride
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2005
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HCN channels
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Rat isolated atria and aorta, effect on the spontaneous beating rate;
Spontaneous firing rate (action potentials per min).
Rabbit isolated sinoatrial node tissue / cell, Spontaneous firing rate
(action potentials per min); electrical activity;
hyperpolarization-activated (If), delayed-rectifier
potassium (IK), T- and L-type calcium
(ICa,L and ICa,T).
Human atrial myocyte, If current.
HCN channel isoforms expressed in HEK293 cells, effect on HCN1 and
HCN4 channels including voltage or currentdependency, reversibility of
the interaction, interaction with open and/or closed channel.
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Conscious normotensive rat, Bradycardic effect.
Conscious Long Evans rats, Cardiac and regional haemodynamic effects,
including heart rate, mean blood pressure, cardiac index, Stroke
index, Peak aortic flow, dF/dtmaz, Total peripheral
conductance, Central venous pressure.
Anesthetized pigs, Hemodynamic and electrocardiographic effects, The
effects on heart rate, LVdP/dt, cardiac output, stroke volume and
total peripheral resistance.
Rat model of left ventricular dysfunction and chronic HF, myocardial
infarction was induced by left coronary artery ligation.
Dog CHF model, intracoronary microembolizations, left ventricular end
systolic volume, left ventricular ejection fraction.
132-AR transgenic mice, effect on survival and on the development of
HF.
Rats pressure overload-induced HF in, aortic banding.
Murine transgenic model, cardiac over-expression of β2-adrenergic
receptors.
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FDA reviews: 206143Orig1s000
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