This information is for research and educational purposes only. No medical recommendations. Products are not approved for human use. For health questions, consult a doctor.

Nebivolol (Bystolic)

The most selective beta blocker with an NO effect - the most tolerable member of its class for anyone training.

3 min read 7 sources

To the sources

Compound approved · since 2007

Summary

At a glance

Sources checked on 26 Oct 2026

Death or hospital admission

-14 %

Heart failure aged 70 and over, 2,128 patients, 31.1 instead of 35.3%¹

Diastolic blood pressure

-11.2 mmHg

Largest drop among the levels, placebo -2.9 mmHg, 909 participants³

Forearm blood flow

+91 %

Infusion into the arm artery, via nitric oxide, the comparison beta blocker without effect⁴

More compound in poor metabolisers

10 -fold

Area under the curve of the active form, broken down via CYP2D6⁵

Nebivolol is a beta blocker that in most people and at usual amounts preferentially blocks the beta-1 receptor of the heart.⁵⁷
It also widens the vessels via nitric oxide. In the human forearm blood flow rose by 91 percent, a nitric oxide blocker clearly dampened this.⁴
In SENIORS the risk of death or cardiovascular hospital admission fell by 14 percent in heart failure patients aged 70 and over, mortality alone not significantly.¹
In a trial with 909 participants it lowered blood pressure clearly more than placebo, side effects were similarly frequent overall.³
It is broken down via CYP2D6. In poor metabolisers and at high amounts it also blocks beta-2. Everything here is the state of research, not a recommendation.⁵

Profile

Updated July 2026

How long does it stay in the body?

Share left after one dose, calculated with a half-life of ~11 hours

Half-life ~11 hours

After 22 hours: 25 %

Hour 11 · 50 %Hour 22 · 25 %Hour 24, next dose · 22 %Hour 33 · 12.5 %Hour 55 · 3.1 %

Simplified model without an absorption phase, half-life from the TPD lexicon. The lexicon gives 10 to 12 hours, we calculate with the middle.

Class

Beta blocker

beta-1 selective, with NO release

Use

Oral

once daily

Half-life

10 to 12 hours

fast metabolisers

Distinctive

Releases nitric oxide

additionally widens vessels

Status

Clinically approved

Contents 12 sections

At a glance
What is nebivolol?
How it works
Use and dosing
What the research shows
Research status
Side effects
Storage
Related compounds
FAQ
Glossary
Sources

What is nebivolol?

Nebivolol is a beta blocker, but a particular one. It is the most selective agent at the beta-1 receptor that exists. It additionally releases nitric oxide in the vascular endothelium. That combination is exactly what sets it apart from the classic members of the class.

Beta-1 selectivity means: it damps the adrenaline effect at the heart while largely leaving beta-2 receptors in bronchi and skeletal muscle alone. The NO effect widens the vessels and lowers peripheral resistance on top. For anyone training, that is the point where this substance separates from bisoprolol.

This information is for research and educational purposes only. No medical advice.

Comparison

Three beta blockers in the lexicon

All three preferentially block the beta-1 receptor of the heart, as stated in the TPD lexicon. Tap a card to open its entry.

Beta-1 selective with NO Nebivolol (Bystolic) Beta-1NO

Beta-1 selective Bisoprolol (Concor) Beta-1 Beta-1 selective, extended release Metoprolol succinate ER (Toprol-XL) Beta-1

Only nebivolol also releases nitric oxide (NO) in the vessels. Part of the blood pressure drop thus comes from vessel widening. ⁷⁴

How it works

A classic beta blocker lowers blood pressure by throttling cardiac output: slower pulse, weaker contraction. The price is a capped maximum heart rate and with it measurably lower endurance performance. Anyone who used to sit at 180 may now reach 150.

Nebivolol does that too, but the NO component additionally lowers peripheral resistance. Part of the pressure reduction therefore does not come from braking the heart but from widening the vessels. In practice: the frequency brake is smaller at equal blood pressure reduction. It is not gone. Anyone doing cardio who still needs a beta blocker does best here, but there is no compromise-free option in this class.

Where it acts

Two receptors, several organs

Tap a point or a card. Colour = target, grey = seen in trials. Beta-2 only at high levels.

Heart

Pulse drops, fewer deaths or admissions in heart failure aged 70 and over¹

Beta-1
Blood vessels

Vessels widen via nitric oxide⁴

NO
Airways

In poor metabolisers and at high amounts beta-2 is blocked too⁵

Beta-2
Liver

Broken down via CYP2D6 and glucuronidation, breakdown products are active too⁵

Observed in trials

Targets in the ChEMBL database⁷

Compound CHEMBL1201731: two recorded mechanisms, type of action on each card.

Beta-1 adrenergic receptor

Gene: ADRB1
UniProt: P08588
ChEMBL: CHEMBL213
Action: Antagonist, preferred at usual amounts

Beta-2 adrenergic receptor

Gene: ADRB2
UniProt: P07550
ChEMBL: CHEMBL210
Action: Antagonist at high levels

Glass heart muscle cells with reddish fibres and blue molecules at their receptors, on the right a glass vessel wall releasing small bubbles of light — Nebivolol slows the heart and widens the vessels via NO. Symbolic image.

Use and dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

Getting started and stepping up, drawn as a staircase
Units on the U-100 syringe for every step
How long one vial lasts

Tablets in a blister, once a day. Symbolic image.

What the research shows

SENIORS (European Heart Journal 2005) is the large outcome trial: over 2,100 patients aged 70 and above with heart failure, randomised to nebivolol or placebo. The combined endpoint of death and cardiovascular hospitalisation fell by 14 percent.

The echo substudy (European Heart Journal 2006) is more interesting in substance. In SENIORS the clinical benefit did not depend on ejection fraction, yet on ultrasound the heart only improved measurably in reduced ejection fraction (smaller volume, higher ejection fraction). In preserved ejection fraction the echo showed no change, so the mechanism of benefit there remains open.

The blood pressure effect is shown by a placebo-controlled dose-ranging trial in the Journal of Clinical Hypertension (2007) in 909 patients: diastolic pressure fell by 8.0 to 11.2 mmHg depending on dose, versus 2.9 mmHg on placebo. The NO mechanism is documented separately: the forearm investigation in the Journal of Pharmacology and Experimental Therapeutics showed directly in humans that the vasodilation runs through an L-arginine/NO dependent pathway. That is not a marketing claim, it was measured.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

Events over 21 months on average¹

SENIORS, 2,128 patients aged 70 and over with heart failure, share with event

Death or cardiovascular hospital admission¹

Placebo 35.3%

Nebivolol 31.1%

Death from any cause¹ not significant

Placebo 18.1%

Nebivolol 15.8%

Hazard ratio 0.86 for the main endpoint. Age, sex and ejection fraction did not change the effect.

Change in blood pressure after up to 12 weeks³

909 participants with mild to moderate high blood pressure, six levels against placebo, values sitting

Diastolic³

Placebo -2.9 mmHg

Nebivolol, smallest drop among the levels -8.0 mmHg

Nebivolol, largest drop among the levels -11.2 mmHg

Systolic³

Placebo +2.2 mmHg

Nebivolol, smallest drop among the levels -4.4 mmHg

Nebivolol, largest drop among the levels -9.5 mmHg

The abstract gives the range over all levels, not which level had which value. On placebo the systolic value rose slightly.

Ejection fraction after 12 months²

Echo substudy of SENIORS, 104 evaluable patients, difference to placebo in percentage points

Reduced pump function² Ejection fraction at most 35%, 43 patients

Difference to placebo 4.6 pp

In addition the heart was 25.8 ml smaller at end-systole. With preserved pump function (61 patients) the echo showed no change, why nebivolol still helped there remains open.

Blood flow in the human forearm⁴

8 participants, infusion into the arm artery, measured by venous occlusion

Rise in blood flow⁴

Nebivolol 91%

Of which blocked by a nitric oxide blocker⁴

Nebivolol 65%

Blocking when L-arginine was added⁴

Nebivolol 15%

L-arginine almost cancelled the blocking, so vessel widening runs via the L-arginine and nitric oxide pathway. Another beta blocker at the same molar amount had no significant effect.

Microscope stage with a petri dish holding a small glass heart, a glass pendulum hanging above it — Symbolic image.

Research status

Where the research stands

Nebivolol has been approved for years. On the registry 128 entries list nebivolol among their interventions. Shown is a selection, SENIORS ran before the registry. As of 26 Oct 2026. ⁶

Preclinical Vessel widening via the L-arginine and nitric oxide pathway
Phase 1 2 trials, 2 completed
Phase 2 2 trials, 2 completed
Phase 3 7 trials, 5 completed
Approval since 2007

171 participants in phase 3 Planned figures for running trials Approved: ChEMBL lists nebivolol with phase 4 as the highest phase and first approval in 2007. The US prescribing information names high blood pressure.⁷

Show all 9 phase 2 and 3 trials on a timelineHide timeline 7 completed 2 running 0 with results

Phase 2

Phase 3

Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026. Phase 1: 2 trials on safety and pharmacokinetics, not shown as bars.

Side effects

Capped maximum heart rate: not a side effect as such, it is the mechanism. Cardio is affected more than lifting.
Fatigue: typical in the first weeks, settles for many.
Bradycardia: resting heart rate below 50 means the dose comes down.
Cold hands and feet: less pronounced than with non-selective beta blockers, but present.
Masked hypoglycaemia: beta blockers damp the warning signs. Relevant for diabetics.
Rebound on stopping: hence always taper.

Tolerability

Frequency in three 12-week high blood pressure trials

Out of 100 participants per group, how many had the event. Three placebo-controlled single-agent trials, according to the US prescribing information.

6 of 100 Placebo

9 of 100 Lowest level

6 of 100 Middle level

7 of 100 Highest levels

Event	Placebo	Lowest level	Middle level	Highest levels
Headache⁵	6%	9%	6%	7%
Fatigue⁵	1%	2%	2%	5%
Dizziness⁵	2%	2%	3%	4%
Nausea⁵	0%	1%	3%	2%
Slow pulse⁵	0%	0%	0%	1%

2.8 percent stopped because of side effects on nebivolol and 2.2 percent on placebo. In the dose-finding trial side effects overall were similarly frequent (46.1 against 40.7 percent).⁵³

Storage

Store dry, at room temperature and protected from light. Keep out of reach of children.

Three white tablet bottles of different sizes and a folded light blue towel on a white shelf — Dry, at room temperature and protected from light. Symbolic image.

Level · Nebivolol (Bystolic)

How the level builds up

One dose per day: each dose adds to what is left of the previous one.

Lexicon: Oral, once daily

Peak 1.28×Trough 0.28×

Day 1 · 2. dose
1.22× of the first dose

Plateau

from Day 1

95 % of the plateau after dose 2

Peak

1.28×

of the first dose

Trough

0.28×

before the next dose

Simplified model, values relative to the first dose, no dosing information. Dashed: the first dose alone, green: the plateau.

Related compounds

Same receptors or a different path: all in the TPD lexicon.

Nebivolol (Bystolic)

Bisoprolol (Concor) Beta-1 selective, without NO

Metoprolol succinate ER (Toprol-XL) Beta-1 selective, as extended release Amlodipine (Norvasc) Different path: calcium channel blocker Ramipril (Altace) Different path: ACE inhibitor Losartan (Cozaar) Different path: angiotensin receptor blocker

FAQ

Common questions about Nebivolol (Bystolic)

Short answers, each backed by the sources below.

How selective is nebivolol?

According to the US prescribing information it acts preferentially on the beta-1 receptor in most people (extensive CYP2D6 metabolisers) and at usual amounts. In poor metabolisers and at higher amounts it blocks beta-1 and beta-2. That is why ChEMBL lists both receptors as targets. Anyone relying on beta-2 in the airways should know this.⁵⁷

What does the nitric oxide effect do?

In the forearm study blood flow rose by 91 percent with nebivolol, another beta blocker at the same molar amount had no significant effect. An inhibitor of nitric oxide formation reduced the widening by 65 percent, with L-arginine added only by 15 percent. Both mirror forms of nebivolol acted alike. So part of the blood pressure drop comes from vessel widening.⁴

What did SENIORS show?

2,128 patients aged 70 and over with heart failure received nebivolol or placebo, for 21 months on average. Death or cardiovascular hospital admission affected 31.1 instead of 35.3 percent (hazard ratio 0.86). Mortality alone fell from 18.1 to 15.8 percent, which was not significant. Age, sex and ejection fraction did not change the effect.¹

Does the heart look better on ultrasound?

Only with reduced pump function. In the echo substudy with 104 evaluable patients ejection fraction rose by 4.6 percentage points against placebo when it was at most 35 percent at baseline. The heart also got smaller. With preserved pump function the echo showed no change after 12 months, the mechanism of benefit remains open there.²

How much does it lower blood pressure?

In a placebo-controlled trial with 909 participants and six levels the diastolic value fell by 8.0 to 11.2 mmHg after up to 12 weeks, by 2.9 mmHg on placebo. The systolic value fell by 4.4 to 9.5 mmHg, on placebo it rose by 2.2 mmHg. Side effects overall were about as frequent as on placebo.³

Is nebivolol approved?

Yes. ChEMBL lists nebivolol with phase 4 as the highest phase and gives 2007 as the year of first approval, the US prescribing information names high blood pressure. Trials are still running on the registry, for example on chest pain without narrowed coronary arteries and on nerve damage in diabetes.⁷⁵⁶

How long does it act and which side effects are there?

According to the US prescribing information the active form has a half-life of about 12 hours in extensive metabolisers and about 19 hours in poor ones, food does not change absorption. The most common side effects are headache and fatigue, at the highest level also dizziness. In the lab uric acid and triglycerides rose and HDL cholesterol fell.⁵

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

Beta blocker: Compound that blocks the beta receptors for adrenaline and noradrenaline. Pulse and blood pressure fall.
Beta-1 selectivity: Preferential action on the beta-1 receptor of the heart, beta-2 in airways and muscles stays largely free.
Bradycardia: Pulse that is too slow, usually below 50 to 60 beats per minute at rest.
CYP2D6: Liver enzyme that breaks down nebivolol. Its activity is inherited and differs between people.
Diastolic value: The lower blood pressure value, measured while the heart relaxes.
Ejection fraction: Share of blood the left ventricle pumps out with each beat. Normal is above 50 percent.
Endothelium: The innermost cell layer of the blood vessels. This is where nitric oxide is made.
Heart failure: The heart no longer pumps enough blood for the body's needs.
L-arginine: Amino acid from which the body makes nitric oxide.
Nitric oxide (NO): Gas produced by the vessel lining. It relaxes vessel muscles and widens the vessels.
Peripheral resistance: The resistance the heart pumps against in the vessels. Wide vessels lower it.

Evidence

Sources

Show all 7 sourcesHide sources 4 Studies1 Trial registry2 Database checked 26 Oct 2026

Studies

Heart failure in people aged 70 and over (SENIORS)
Flather et al., European Heart Journal, 2005

DOI 10.1093/eurheartj/ehi115 PMID 15642700

Checked 26 Oct 2026 via doi.org, Crossref, PubMed
Echocardiography with preserved and reduced pump function (SENIORS)
Ghio et al., European Heart Journal, 2006

DOI 10.1093/eurheartj/ehi735 PMID 16443607

Checked 26 Oct 2026 via doi.org, Crossref, PubMed
High blood pressure: dose finding against placebo with 909 participants
Weiss et al., Journal of Clinical Hypertension, 2007

DOI 10.1111/j.1524-6175.2007.06679.x PMID 17786067

Checked 26 Oct 2026 via doi.org, Crossref, PubMed
Forearm vessel widening via the L-arginine and nitric oxide pathway
Cockcroft et al., Journal of Pharmacology and Experimental Therapeutics, 1995

DOI 10.1016/s0022-3565(25)10549-1 PMID 7562470

Checked 26 Oct 2026 via doi.org, Crossref, PubMed (Titel, Datensatz ohne DOI)

Trial registry

All trials on ClinicalTrials.gov
ClinicalTrials.gov, U.S. National Library of Medicine

Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

US approval and prescribing information (Drugs@FDA)
U.S. Food and Drug Administration, NDA 021742

Checked 26 Oct 2026 via openFDA (drugsfda, label)
Mechanism and approval in ChEMBL
ChEMBL, EMBL-EBI (CHEMBL1201731)

Checked 26 Oct 2026 via ChEMBL