Nebivolol

Nebivolol

Clinical data
Trade names	Nebilet, Bystolic
AHFS/Drugs.com	Monograph
MedlinePlus	a608029
License data	US FDA: Nebivolol
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	Oral
ATC code	C07AB12 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Protein binding	98%
Metabolism	Hepatic (CYP2D6-mediated)
Biological half-life	10 hours
Excretion	Renal and fecal
Identifiers
IUPAC name (1RS,1' RS)-1,1'-[(2RS,2' SR)-bis(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)]-2,2'-iminodiethanol OR 1-(6-Fluorochroman-2-yl)-{[2-(6-fluorochroman-2-yl)-2-hydroxy-ethyl]amino}ethanol OR 2,2'-Azanediylbis(1-(6-fluorochroman-2-yl)ethanol) OR 1-(6-Fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-{[2-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-hydroxyethyl]amino}ethan-1-ol
CAS Number	118457-14-0 N
PubChem CID	71301
IUPHAR/BPS	7246
DrugBank	DB04861 Y
ChemSpider	64421 Y
UNII	030Y90569U
KEGG	D05127 Y
ChEMBL	CHEMBL434394 Y
Chemical and physical data
Formula	C22H25F2NO4
Molar mass	405.435 g/mol
3D model (Jmol)	Interactive image
SMILES Fc4cc1c(OC(CC1)C(O)CNCC(O)C3Oc2ccc(F)cc2CC3)cc4
InChI InChI=1S/C22H25F2NO4/c23-15-3-7-19-13(9-15)1-5-21(28-19)17(26)11-25-12-18(27)22-6-2-14-10-16(24)4-8-20(14)29-22/h3-4,7-10,17-18,21-22,25-27H,1-2,5-6,11-12H2 Y Key:KOHIRBRYDXPAMZ-UHFFFAOYSA-N Y
NY (what is this?)

Nebivolol is a β₁ receptor blocker with nitric oxide-potentiating vasodilatory effect used in treatment of hypertension and, in Europe, also for left ventricular failure. It is highly cardioselective under certain circumstances.

Beta blockers help patients with cardiovascular disease by blocking β receptors, while many of the side-effects of these medications are caused by their blockade of β2 receptors. For this reason, beta blockers that selectively block β1 adrenergic receptors (termed cardioselective or β1-selective beta blockers) produce fewer adverse effects (for instance, bronchoconstriction) than those drugs that non-selectively block both β1 and β2 receptors.

In a laboratory experiment conducted on biopsied heart tissue, nebivolol proved to be the most β1-selective of the β-blockers tested, being approximately 3.5 times more β1-selective than bisoprolol. However, the drug's receptor selectivity in humans is more complex and depends on the drug dose and the genetic profile of the patient taking the medication. The drug is highly cardioselective at 5 mg. In addition, at doses above 10 mg, nebivolol loses its cardioselectivity and blocks both β1 and β2 receptors. (While the recommended starting dose of nebivolol is 5 mg, sufficient control of blood pressure may require doses up to 40 mg). Furthermore, nebivolol is also not cardioselective when taken by patients with a genetic makeup that makes them "poor metabolizers" of nebivolol (and other drugs) or with CYP2D6 inhibitors. As many as 1 in 10 whites and even more blacks are poor CYP2D6 metabolizers and therefore might benefit less from nebivolol's cardioselectivity although currently there are no directly comparable studies.

Nebivolol is unique as a beta-blocker. Unlike carvedilol, it has a nitric oxide (NO)-potentiating, vasodilatory effect. Along with labetalol, celiprolol and carvedilol, it is one of four beta blockers to cause dilation of blood vessels in addition to effects on the heart. However, recent studies question the clinical relevance of this property to Nebivolol's efficacy.