Nebivolol

Nebivolol hydrochloride selectively inhibits β1- adrenergic receptor with IC50 of 0.8 nM.

Differential Metabolic Effects of Beta-Blockers: an Updated Systematic Review of Nebivolol.[Pubmed:28283926]

Curr Hypertens Rep. 2017 Mar;19(3):22.

Blood pressure management in hypertensive patients with metabolic abnormalities is challenging, since many of the antihypertensive drugs adversely affect metabolism. Besides effective control of blood pressure in patients with hypertension, third-generation beta-blockers such as Nebivolol offer additional benefits for central hemodynamics and neutral or beneficial effects on metabolism. Emerging clinical data suggest that Nebivolol also has similar effects on metabolism in obese hypertensive and hypertensive diabetic patients. The present article will provide a systematic analysis of the pathophysiological links among hypertension, insulin resistance, and metabolic syndrome. We will also summarize the available clinical evidence regarding the metabolic effects of beta-blockers in hypertensive patients, with an emphasis on Nebivolol. Nebivolol exerts neutral or beneficial effects on insulin sensitivity and lipid metabolism in hypertensive patients, owing to its nitric oxide-mediated vasodilatory and antioxidative properties. Thus, Nebivolol could be a favorable therapeutic option for the treatment of hypertension in patients with impaired glucose and lipid metabolism.

The Comparison of the Effects of Nebivolol and Metoprolol on Erectile Dysfunction in the Cases with Coronary Artery Bypass Surgery.[Pubmed:28302931]

Ann Thorac Cardiovasc Surg. 2017 Apr 20;23(2):91-95.

PURPOSE: Beta-blocker use is common in the cases with coronary artery bypass surgery. According to the literature, beta-blockers have positive effects but may cause erectile dysfunction (ED). The most commonly used beta-blockers in ischemic cardiac disease are Nebivolol and metoprolol. In our clinic, we aimed to compare the effects of Nebivolol and metoprolol succinate on ED in the sexually active cases with coronary artery bypass surgery. METHODS: In our clinic, a total of 119 patients with coronary artery bypass surgery were included in the study. International Index of Erectile Function (IIEF-5) Test was used to evaluate whether the patients had ED and to grade the cases. RESULTS: No significant difference was found in terms of anti-ischemic efficacy between metoprolol succinate and Nebivolol in the postoperative period; however, the incidence of any grade ED was %85.96 in Group 1, %83.87 in Group 2. This difference was considered as statistically significant (p = 0.036). CONCLUSION: Beta-blocker use increases the risk of ED in cases with ischemic cardiac disease. We suggest that the complaints of ED could be less frequent with Nebivolol use in sexually active cases with ischemic cardiac disease.

Photolytic degradation of the beta-blocker nebivolol in aqueous solution.[Pubmed:28340419]

Water Res. 2017 Jun 1;116:211-219.

Nebivolol (NEB) is one of the top-sold prescription drugs belonging to the third generation of beta-blockers. However, so far, occurrence data in the environment are lacking. Within this study NEB has been found for the first time in effluent samples of wastewater treatment plants in Germany with an average concentration of 13 ng L(-1). Its photodegradation behavior in the environment and in technical processes is largely unknown. To fill this gap, three different UV treatment procedures (UV-C at 254 nm, UV-B at 312 nm and UV-A at 365 nm) were investigated in three different matrices: pure water, pure water in presence of the hydroxyl radical (OH) scavenger tert.-butanol and real wastewater. No elimination was observed during UV-A treatment. In contrast, NEB degradation during UV-B and UV-C treatment followed pseudo first order reaction kinetics, with highest removal rate during UV-C treatment in pure water (k = 7.8 x 10(-4) s(-1)). The rate constant for UV-C irradiation decreased to 2.9 x 10(-4) s(-1) in the presence of the OH scavenger and in the presence of the wastewater matrix. The rate constant for the UV-B lamp was 4.4 x 10(-4) s(-1), Three transformation products were identified after UV-B and UV-C photolytic degradation using high resolution mass spectrometry. The main photoreaction is the substitution of the fluorine atoms of NEB by hydroxyl groups. A photolytic cleavage of the CF bond can be excluded as the high bond dissociation energy of aromatic CF bonds (525 kJ mol(-1)), exceeds the energy of electromagnetic radiation applied in the present study (>/=254 nm, i.e., max. 471 kJ E(-1)). The quantum yields for NEB degradation for the UV-C lamp achieved in pure water, the OH scavenged system and wastewater matrix were Phideg = 0.53, 0.19 and 0.22, respectively. For UV-B Phideg was 0.023 +/- 0.003, noticeable differences in quantum yield were not found. The photooxidation involves reactive oxygen species such as superoxide and singlet oxygen. These oxidative species may be formed upon reaction of photo-excited NEB with oxygen.

Nebivolol attenuates cerebral vasospasm both by increasing endothelial nitric oxide and by decreasing oxidative stress in an experimental subarachnoid haemorrhage.[Pubmed:28335640]

Br J Neurosurg. 2017 Aug;31(4):439-445.

OBJECTIVE: Evidence suggests that reduction of nitric oxide (NO) bioavailability due to oxidative stress plays a central role in the pathophysiology of cerebral vasospasm after subarachnoid haemorrhage (SAH). To prevent SAH-induced cerebral vasospasm, therefore we used Nebivolol hydrochloride as a NO-mediated vasodilator and an antioxidant drug in an experimental rat model of SAH. MATERIALS AND METHODS: Forty female Wistar rats were divided into control, SAH, SAH plus placebo, and SAH plus Nebivolol groups. Starting six hours after inducing SAH, 5 mg/kg of Nebivolol hydrochloride and of pharmaceutical excipients of Nebivolol was given orally once daily for five days to SAH plus Nebivolol and SAH plus placebo groups, respectively. The lumen diameter and vessel wall thickness of the basilar artery were measured in brain sections. The serum and brain supernatant levels of nitric oxide (NO) were analysed. The brain supernatant levels of intrinsic antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as markers of the antioxidant status. RESULTS: Nebivolol administration attenuated cerebral vasospasm both by increasing NO levels and by decreasing oxidative stress. Our study also demonstrated that Nebivolol administration reverses SAH created imbalance between SOD and GSH-Px by increasing GSH-Px activity relative to SOD. CONCLUSIONS: Nebivolol attenuates the cerebral vasospasm after SAH both increasing NO levels and decreasing oxidative stress. Therefore, it may promise to prevent SAH-induced cerebral vasospasm as an anti-spasmodic and anti-oxidant agent.