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International Journal of Molecular... Sep 2022Propranolol, a non-cardioselective β blocker, is most commonly recognised for its application in the therapy of various cardiovascular conditions, such as hypertension,... (Review)
Review
Propranolol versus Other Selected Drugs in the Treatment of Various Types of Anxiety or Stress, with Particular Reference to Stage Fright and Post-Traumatic Stress Disorder.
Propranolol, a non-cardioselective β blocker, is most commonly recognised for its application in the therapy of various cardiovascular conditions, such as hypertension, coronary artery disease, and tachyarrhythmias. However, due to its ability to cross the blood-brain barrier and affinity towards multiple macromolecules, not only adrenoreceptors, it has also found application in other fields. For example, it is one of the very few medications successfully applied in the treatment of stage fright. This review focuses on the application of propranolol in the treatment of various types of anxiety and stress, with particular reference to stage fright and post-traumatic stress disorder (PTSD). Both mechanisms of action as well as comparison with other therapies are presented. As those indications for propranolol are, in most countries, considered off-label, this review aims to gather information that can be useful while making a decision about the choice of propranolol as a drug in the treatment of those mental conditions.
Topics: Anxiety; Anxiety Disorders; Humans; Propranolol; Stress Disorders, Post-Traumatic
PubMed: 36077489
DOI: 10.3390/ijms231710099 -
Critical Care (London, England) Jun 2023To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI).
BACKGROUND
Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit.
METHODS
This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16-64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study.
RESULTS
Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (- 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes.
CONCLUSION
Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.
Topics: Humans; Propranolol; Clonidine; Pilot Projects; Treatment Outcome; Brain Injuries, Traumatic; Adrenergic Agents
PubMed: 37296432
DOI: 10.1186/s13054-023-04479-6 -
Ugeskrift For Laeger Mar 2019
Topics: Adrenergic beta-Antagonists; Anxiety Disorders; Humans; Propranolol
PubMed: 30931879
DOI: No ID Found -
International Journal of Clinical... 2022This study aims to evaluate the effects of bevacizumab and propranolol from the point of view of a possible antiangiogenic effect in a model of primary nasal polyp (NP)...
OBJECTIVE
This study aims to evaluate the effects of bevacizumab and propranolol from the point of view of a possible antiangiogenic effect in a model of primary nasal polyp (NP) tissue culture.
METHODS
NP samples of 21 patients and normal healthy nasal mucosa samples of 7 patients were cultured. Samples were divided into four groups as follows (healthy nasal mucosa, NP without any treatment, NP treated with propranolol, NP treated with bevacizumab). Cultured tissues were formalin fixed and paraffin embedded. Tissue sections and immunohistochemical VEGF-A, angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2) expressions were evaluated. ELISA was also performed for each one of them.
RESULTS
Both propranolol and bevacizumab significantly decreased the expressions of VEGF-A and Ang-1, and they significantly increased the expression of Ang-2 in comparison to the control NP group. In the healthy nasal mucosa group, no significant expression of VEGF-A was seen, a slight (+) Ang-1 expression, and a high (+++) Ang-2 expression were observed.
CONCLUSION
Bevacizumab and propranolol exert an antiangiogenic effect on NP tissues, mainly by decreasing VEGF-A and Ang-1 expression, increasing Ang-2 expression.
Topics: Humans; Nasal Polyps; Bevacizumab; Propranolol; Vascular Endothelial Growth Factor A; Enzyme-Linked Immunosorbent Assay
PubMed: 36304979
DOI: 10.1155/2022/6174664 -
World Journal of Emergency Surgery :... 2017The objective of this systematic review was to determine the effectiveness and safety of propranolol compared to placebo or usual care for improving clinical relevant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The objective of this systematic review was to determine the effectiveness and safety of propranolol compared to placebo or usual care for improving clinical relevant outcomes in severely burned patients (TBSA >20%).
METHODS
Relevant articles from randomized controlled trials were identified by a literature search in MEDLINE, EMBASE, and CENTRAL. We included trials involving patients with a severe burn (>20% of total body surface area affected). Trials were eligible if they evaluated propranolol and compared to usual care or placebo. Two investigators independently assessed articles for inclusion and exclusion criteria and selected studies for the final analysis. We conducted a meta-analysis using a random-effects model.
RESULTS
We included ten studies in our systematic review. These studies randomized a total of 1236 participants. There were no significant differences between propranolol and placebo with respect to mortality (RD -0.02 [95% CI -0.06 to 0.02]), sepsis (RD -0.03 [95% CI -0.09 to 0.04]), and the overall hospital stay (MD -0.37 [-4.52 to 3.78]). Propranolol-treated adults had a decrease in requirements of blood transfusions (MD -185.64 [95% CI -331.06 to -40.43]) and a decreased heart rate (MD -26.85 [95% CI -39.95 to -13.75]).
CONCLUSIONS
Our analysis indicates that there were no differences in mortality or sepsis in severely burned patients treated with propranolol compared with those who had usual care or placebo. However, the use of propranolol in these patients resulted in lower requirements of blood transfusion and lower values of heart rate. The evidence synthesized in this systematic review is limited to conclude that propranolol reduces the length of hospital stay among severely burned patients. Future trials should assess the impact of propranolol on clinically relevant outcomes such as mortality and adverse events.
Topics: Adrenergic beta-Antagonists; Burns; Humans; Patient Safety; Propranolol
PubMed: 28265298
DOI: 10.1186/s13017-017-0124-7 -
International Journal of Molecular... May 2022Infantile hemangioma (IH) is the most common infantile tumor, affecting 5-10% of newborns. Propranolol, a nonselective β-adrenergic receptor (ADRB) antagonist, is...
Infantile hemangioma (IH) is the most common infantile tumor, affecting 5-10% of newborns. Propranolol, a nonselective β-adrenergic receptor (ADRB) antagonist, is currently the first-line treatment for severe IH; however, both its mechanism of action and its main cellular target remain poorly understood. Since betablockers can antagonize the effect of natural ADRB agonists, we postulated that the catecholamine produced in situ in IH may have a role in the propranolol response. By quantifying catecholamines in the IH tissues, we found a higher amount of noradrenaline (NA) in untreated proliferative IHs than in involuted IHs or propranolol-treated IHs. We further found that the first three enzymes of the catecholamine biosynthesis pathway are expressed by IH cells and that their levels are reduced in propranolol-treated tumors. To study the role of NA in the pathophysiology of IH and its response to propranolol, we performed an in vitro angiogenesis assay in which IH-derived endothelial cells, pericytes and/or telocytes were incorporated. The results showed that the total tube formation is sensitive to propranolol only when exogenous NA is added in the three-cell model. We conclude that the IH's sensitivity to propranolol depends on crosstalk between the endothelial cells, pericytes and telocytes in the context of a high local amount of local NA.
Topics: Adrenergic beta-Antagonists; Endothelial Cells; Hemangioma; Humans; Infant; Infant, Newborn; Neuroendocrine Tumors; Norepinephrine; Propranolol
PubMed: 35563552
DOI: 10.3390/ijms23095140 -
International Journal of Molecular... Jul 2022Propranolol is a competitive non-selective beta-receptor antagonist that is available on the market as a racemic mixture. In the present study, glucuronidation of...
Propranolol is a competitive non-selective beta-receptor antagonist that is available on the market as a racemic mixture. In the present study, glucuronidation of propranolol and its equipotent phase I metabolite 4-hydroxypropranolol by all 19 members of the human UGT1 and UGT2 families was monitored. UGT1A7, UGT1A9, UGT1A10 and UGT2A1 were found to glucuronidate propranolol, with UGT1A7, UGT1A9 and UGT2A1 mainly acting on ()-propranolol, while UGT1A10 displays the opposite stereoselectivity. UGT1A7, UGT1A9 and UGT2A1 were also found to glucuronidate 4-hydroxypropranolol. In contrast to propranolol, 4-hydroxypropranolol was found to be glucuronidated by UGT1A8 but not by UGT1A10. Additional biotransformations with 4-methoxypropanolol demonstrated different regioselectivities of these UGTs with respect to the aliphatic and aromatic hydroxy groups of the substrate. Modeling and molecular docking studies were performed to explain the stereoselective glucuronidation of the substrates under study.
Topics: Glucuronides; Glucuronosyltransferase; Humans; Microsomes, Liver; Molecular Docking Simulation; Propranolol; UDP-Glucuronosyltransferase 1A9
PubMed: 35806479
DOI: 10.3390/ijms23137476 -
Scientific Reports Sep 2022Osteosarcoma is still associated with limited response to standard-of-care therapy and alarmingly elevated mortality rates, especially in low- and middle-income...
Osteosarcoma is still associated with limited response to standard-of-care therapy and alarmingly elevated mortality rates, especially in low- and middle-income countries. Despite multiple efforts to repurpose β-blocker propranolol in oncology, its potential application in osteosarcoma management remains largely unexplored. Considering the unsatisfied clinical needs of this aggressive disease, we evaluated the antitumoral activity of propranolol using different in vitro and in vivo osteosarcoma preclinical models, alone or in addition to chemotherapy. Propranolol significantly impaired cellular growth in β2-adrenergic receptor-expressing MG-63 and U-2OS cells, and was capable of blocking growth-stimulating effects triggered by catecholamines. siRNA-mediated ADRB2 knockdown in MG-63 cells was associated with decreased cell survival and a significant attenuation of PPN anti-osteosarcoma activity. Direct cytostatic effects of propranolol were independent of apoptosis induction and were associated with reduced mitosis, G0/G1 cell cycle arrest and a significant down-regulation of cell cycle regulator Cyclin D1. Moreover, colony formation, 3D spheroid growth, cell chemotaxis and capillary-like tube formation were drastically impaired after propranolol treatment. Interestingly, anti-migratory activity of β-blocker was associated with altered actin cytoskeleton dynamics. In vivo, propranolol treatment (10 mg/kg/day i.p.) reduced the early angiogenic response triggered by MG-63 cells in nude mice. Synergistic effects were observed in vitro after combining propranolol with chemotherapeutic agent cisplatin. Sustained administration of propranolol (10 mg/kg/day i.p., five days a week), alone and especially in addition to low-dose metronomic cisplatin (2 mg/kg/day i.p., three times a week), markedly reduced xenograft progression. After histological analysis, propranolol and cisplatin combination resulted in low tumor mitotic index and increased tumor necrosis. β-blockade using propranolol seems to be an achievable and cost-effective therapeutic approach to modulate osteosarcoma aggressiveness. Further translational studies of propranolol repurposing in osteosarcoma are warranted.
Topics: Animals; Apoptosis; Bone Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cisplatin; Heterografts; Humans; Mice; Mice, Nude; Osteosarcoma; Propranolol; Xenograft Model Antitumor Assays
PubMed: 36075937
DOI: 10.1038/s41598-022-18324-3 -
Neurobiology of Learning and Memory Apr 2016Posttraumatic stress disorder (PTSD) has been described as the only neuropsychiatric disorder with a known cause, yet effective behavioral and pharmacotherapies remain... (Review)
Review
Posttraumatic stress disorder (PTSD) has been described as the only neuropsychiatric disorder with a known cause, yet effective behavioral and pharmacotherapies remain elusive for many afflicted individuals. PTSD is characterized by heightened noradrenergic signaling, as well as a resistance to extinction learning. Research aimed at promoting more effective treatment of PTSD has focused on memory erasure (disrupting reconsolidation) and/or enhancing extinction retention through pharmacological manipulations. Propranolol, a β-adrenoceptor antagonist, has received considerable attention for its therapeutic potential in PTSD, although its impact on patients is not always effective. In this review, we briefly examine the consequences of β-noradrenergic manipulations on both reconsolidation and extinction learning in rodents and in humans. We suggest that propranolol is effective as a fear-reducing agent when paired with behavioral therapy soon after trauma when psychological stress is high, possibly preventing or dampening the later development of PTSD. In individuals who have already suffered from PTSD for a significant period of time, propranolol may be less effective at disrupting reconsolidation of strong fear memories. Also, when PTSD has already developed, chronic treatment with propranolol may be more effective than acute intervention, given that individuals with PTSD tend to experience long-term, elevated noradrenergic hyperarousal.
Topics: Adrenergic beta-Antagonists; Animals; Behavior, Animal; Disease Models, Animal; Extinction, Psychological; Fear; Humans; Memory; Propranolol; Rats; Stress Disorders, Post-Traumatic
PubMed: 26808441
DOI: 10.1016/j.nlm.2016.01.009 -
Journal of Psychiatry & Neuroscience :... Jul 2013Considering the pivotal role of negative emotional experiences in the development and persistence of mental disorders, interfering with the consolidation/reconsolidation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Considering the pivotal role of negative emotional experiences in the development and persistence of mental disorders, interfering with the consolidation/reconsolidation of such experiences would open the door to a novel treatment approach in psychiatry. We conducted a meta-analysis on the experimental evidence regarding the capacity of the ß-blocker propranolol to block the consolidation/reconsolidation of emotional memories in healthy adults.
METHODS
Selected studies consisted of randomized, double-blind experiments assessing long-term memory for emotional material in healthy adults and involved at least 1 propranolol and 1 placebo condition. We searched PsycInfo, PubMed, Web of Science, Cochrane Central, PILOTS, Google Scholar and clinicaltrials.org for eligible studies from the period 1995-2012. Ten consolidation (n = 259) and 8 reconsolidation (n = 308) experiments met the inclusion criteria. We calculated effect sizes (Hedges g) using a random effects model.
RESULTS
Compared with placebo, propranolol given before memory consolidation reduced subsequent recall for negatively valenced stories, pictures and word lists (Hedges g = 0.44, 95% confidence interval [CI] 0.14-0.74). Propranolol before reconsolidation also reduced subsequent recall for negatively valenced emotional words and the expression of cue-elicited fear responses (Hedges g = 0.56, 95% CI 0.13-1.00).
LIMITATIONS
Limitations include the moderate number of studies examining the influence of propranolol on emotional memory consolidation and reconsolidation in healthy adults and the fact that most samples consisted entirely of young adults, which may limit the ecological validity of results.
CONCLUSION
Propranolol shows promise in reducing subsequent memory for new or recalled emotional material in healthy adults. However, future studies will need to investigate whether more powerful idiosyncratic emotional memories can also be weakened and whether this weakening can bring about long-lasting symptomatic relief in clinical populations, such as patients with posttraumatic stress or other event-related disorders.
Topics: Adult; Dose-Response Relationship, Drug; Emotions; Female; Humans; Male; Memory, Long-Term; Mental Recall; Middle Aged; Propranolol; Retention, Psychology; Sex Characteristics
PubMed: 23182304
DOI: 10.1503/jpn.120111