Nebivolol

• (? R *, α'R *, 2R *, 2 'S *) - α, α' - [ iminobis (methylene) ] bis [ 6 - fluoro-3 ,4-dihydro- 2H-1- benzo- pyran-2 -methanol ]
• (? R *, α'R *, 2R *, 2 'S *) - α, α' - [ iminobis (methylene )] - bis [ 6- fluorchroman -2-methanol ]

C07AB12

β -adrenergic receptor blocker

Highly selective blockade of β1 - receptors and NO -dependent Gefäßvasodilatation

Template: Infobox chemical / molecular formula search available

Nebivolol is a drug from the group of selective β1 - adrenergic receptor ( beta-blockers ) and is used to reduce a high blood pressure.

Operation

Nebivolol is composed of a racemic mixture of two enantiomers (? R, α ' R, 2R, 2 'S ) - and ( αS, α ' S, 2S, 2 ' R) - nebivolol (racemate ). Both enantiomers are involved in the effect. The active stereoisomer ( eutomer ) is the (? R, α ' R, 2R, 2' S)-form of nebivolol.

Representing the third generation of beta-blockers nebivolol has two mechanisms of action: in addition to the highly selective blockade of β1 -adrenoceptors ( which is characteristic for representatives of the second generation) by D - nebivolol has an additional L- nebivolol on the endothelial cells of vessels. It has a vasodilating action due to nitric oxide release in endothelial cells, in contrast to conventional beta-blockers. There is, consequently, a pronounced improved endothelial function, and improvement of hemodynamics. This mode of action leads, in comparison to conventional beta-blockers, in an improved circulation in the macro and micro vessels. These vasodilating effects of beta-blockers has also celiprolol. Whether this specificity has a positive impact on morbidity and mortality, but could not be occupied until 2012 by studies.

Areas of application (indications )

Nebivolol is indicated for the treatment of hypertension and as an adjunct to standard therapies for the treatment of stable mild to moderate chronic heart failure (heart failure ) in elderly patients (over 70 years).

Contraindications ( contraindications)

Nebivolol should not be used in hepatic insufficiency or hepatic impairment, acute heart failure, bronchospasm and bronchial asthma, bradycardia, severe peripheral circulatory disorders, as in Raynaud's disease ("white finger ", white and numb toes) and hypotension.

Side effects

As an adverse reaction may occur: headache, dizziness, nausea, fatigue, edema and sometimes nightmares, blurred vision, slow heart rate ( bradycardia).

Development and marketing

Nebivolol was jointly developed by Menarini and Janssen Pharmaceutica as beta blockers 3rd generation. In Germany, nebivolol has been approved for oral administration in the field of indication hypertension 1996 under the name Bystolic is used as a drug, and came in 1997 to the market.

For the market in the U.S. and Canada, Janssen Pharmaceutica licensed the drug from 2001 to Mylan Laboratories.

Beginning of 2008 brought in Germany the company Hexal AG and Sandoz, the first nebivolol generics on the market. Since then wrangling over the legality, as the originator Berlin-Chemie to October 2010, makes patent protection claims against several generic companies but had filed nullity actions. Explosive issue of the battle was against the background that health insurance companies had concluded with the generic companies discount contracts, what pharmacies undertook to supply the one hand, on the other hand thus exposed but possible actions for damages by Berlin-Chemie. The Federal Patent Court declared in June 2008, the patent for Bystolic null and void, and the process went before the Federal Court, where it is still pending. Middlemen ( wholesalers ) sell because of the legal uncertainty continues to exist no nebivolol generics. After Nebivolol was deleted from the discount agreements, participated in the course of 2009, several generic companies their nebivolol drug from the market; In addition to the pending patent disputes play, according to the company economic reasons by the pressure of fixed reimbursement a role. Since the patent has expired but in late October 2010, the generics market is now open to all competitors.

Trade names

Bystolic (USA), Hypoloc (A, DK, IS, IRE, NO, SE, UK), Lobivon ( GR, ES), Bystolic (D, CH, PT), Nebilox (IT), Nobiten ( LUX ), nebivolol ( A) Temerit (FR ), various generic (A, D)