Nebivolol Chemical Properties

Melting point:

155-156°C

Boiling point:

600.5±55.0 °C(Predicted)

Density 

1.309

storage temp. 

-20°C Freezer

solubility 

DMSO (Slightly), Methanol (Slightly, Heated)

pka

pKa 8.22(H2O,t =25±1,Iundefined,Ar) (Uncertain)

form 

Solid

color 

White to Off-White

Nebivolol Usage And Synthesis

History

The development of nebivolol began in the early 1980s, led by a research team at Janssen Pharmaceutica in Belgium. The design goal was to develop a novel cardiovascular drug with high β1-adrenergic receptor selectivity. The compound was successfully synthesized in the early 1990s, and its unique pharmacological characteristics lie in its dual mechanism of action: it is not only a highly potent third-generation β-blocker, but also promotes nitric oxide (NO)-mediated vasodilation by activating endothelial nitric oxide synthase (eNOS). This innovative mechanism of action was elucidated in the work of early researchers such as P. M. Vanhoutte. After systematic preclinical and clinical development, nebivolol received its first regulatory approval in Germany in 1997 for the treatment of essential hypertension. Subsequent extensive studies further established its clinical advantages in improving endothelial function and exhibiting better tolerability, distinguishing it from traditional β-blockers as a modern antihypertensive drug with vasodilatory properties.

Uses

Nebivolol is a cardioselective beta-1 receptor blocking agent.

Uses

Antihypertensive (β-blocker).

Definition

ChEBI: (R,S,S,S)-nebivolol is a 2,2'-iminobis[1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanol] that has (1S,1'S,2R,2'S)-configuration. It is a conjugate base of a (R,S,S,S)-nebivolol(1+). It is an enantiomer of a (S,R,R,R)-nebivolol.

Clinical Use

Beta-adrenoceptor blocker:
Essential hypertension
Adjunct in heart failure

Drug interactions

Potentially hazardous interactions with other drugs
Anaesthetics: enhanced hypotensive effect.
Analgesics: NSAIDs antagonise hypotensive effect.
Anti-arrhythmics: increased risk of myocardial depression and bradycardia; increased risk of bradycardia, myocardial depression and AV block with amiodarone; increased risk of myocardial depression and bradycardia with flecainide.
Antidepressants: enhanced hypotensive effect with MAOIs.
Antihypertensives; enhanced hypotensive effect; increased risk of withdrawal hypertension with clonidine; increased risk of first dose hypotensive effect with post-synaptic alpha-blockers such as prazosin.
Antimalarials: increased risk of bradycardia with mefloquine.
Antipsychotics enhanced hypotensive effect with phenothiazines.
Calcium-channel blockers: increased risk of bradycardia and AV block with diltiazem; hypotension and heart failure possible with nifedipine and nisoldipine; asystole, severe hypotension and heart failure with verapamil.
Cytotoxics: possible increased risk of bradycardia with crizotinib.
Diuretics: enhanced hypotensive effect.
Fingolimod: possibly increased risk of bradycardia. Moxisylyte: possible severe postural hypotension.
Sympathomimetics: severe hypertension with adrenaline and noradrenaline and possibly with dobutamine.

Metabolism

Nebivolol is extensively metabolised in the liver by acyclic and aromatic hydroxylation, N-dealkylation, and glucuronidation. Hydroxylation is by cytochrome P450 isoenzyme CYP2D6, partly to active hydroxy-metabolites. It is excreted in the urine and faeces, almost entirely as metabolites.

Nebivolol(118457-14-0)Related Product Information

• (+)-Nebivolol
• Nebivolol
• Nebivolol
• 3-(4-FLUOROPHENOXY)PROPAN-1-AMINE HYDROCHLORIDE