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Brain and Behavior Mar 2023Propranolol, a nonselective beta-adrenergic blocker, has long been used as one of the standard treatments for essential tremor (ET). Repetitive transcranial magnetic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Propranolol, a nonselective beta-adrenergic blocker, has long been used as one of the standard treatments for essential tremor (ET). Repetitive transcranial magnetic stimulation (rTMS) has also been used for a long time as a substitution therapy for ET patients.
OBJECTIVE
The main aim of this study was to evaluate the antitremor effect of 1-Hz (low-frequency) cerebellar rTMS and compare it to the use of propranolol in ET patients.
METHODS
In this single-blinded, randomized, controlled pilot study, a total of 38 patients with ET were randomized into two groups. One group (n = 20) received 1200 pulses of 1-Hz rTMS at an intensity of 90% of the resting motor threshold to the bilateral cerebellar region for 10 days. Another group (n = 18) received oral propranolol for 30 days. The initial dose was 30 mg/day, which was increased to 60 mg/day after 5 days, then to 90 mg/day on the 11th day, and continued thereafter for 20 days. The Fahn-Tolosa-Marin (FTM) clinical scale was assessed at baseline and at days 5, 10, and 30 to evaluate tremor severity, specific motor tasks, and functional disability.
RESULTS
Low-frequency rTMS of the cerebellum significantly improved tremor severity, specific motor tasks (writing, spiral drawing, and pouring), and FTM total scores on days 10 and 30. Nevertheless, we found no significant difference in functional disability at any point in time (p > .05). There were no statistically significant differences in FTM Part A, Part B, Part C scores and total scores of patients in propranolol group on days 5 and 10 compared with before treatment (p > .05). However, FTM total scores and FTM Part A, Part B, and Part C scores were significantly improved for patients when the dose of propranolol was 90 mg/day on day 30. Our study showed that there was no statistically significant difference in the total FTM scores and FTM Part A, Part B, and Part C scores between rTMS and propranolol on days 5, 10, and 30 (p > .05).
CONCLUSION
We conclude that both cerebellar low-frequency rTMS and propranolol could be effective treatment options for patients with ET, but it is not clear which method is more effective.
Topics: Humans; Essential Tremor; Transcranial Magnetic Stimulation; Propranolol; Tremor; Cerebellum; Treatment Outcome
PubMed: 36806734
DOI: 10.1002/brb3.2926 -
Annals of Clinical and Translational... Sep 2022Assess whether propranolol modulates the trigeminovascular system in both men and women. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Assess whether propranolol modulates the trigeminovascular system in both men and women.
METHODS
We investigated the effect of propranolol (80 mg, 90 min after oral administration, corresponding to T ) on the increase in dermal blood flow of the forehead skin (innervated by the trigeminal nerve) by capsaicin application (0.6 mg/mL) and electrical stimulation (0.2-1.0 mA) before and after placebo (grapefruit juice) or propranolol (oral solution diluted in grapefruit juice) in a randomized, double-blind, placebo-controlled cross-over study, including healthy males (n = 10) and females on contraceptives (n = 11). Additionally, we compared our results with data from the Dutch IADB.nl prescription database by analyzing the change in triptan use after propranolol prescription in a population similar to our dermal blood flow study subjects (males and females, 20-39 years old).
RESULTS
Dermal blood flow responses to capsaicin were significantly attenuated after propranolol, but not after placebo. When stratifying by sex, no significant changes in the capsaicin-induced dermal blood flow were observed in females after propranolol, whereas they remained significant in males. Dermal blood flow responses to electrical stimulation were not modified in any case. In our prescription database study, after propranolol, a more pronounced decrease in triptan use was observed in male patients than in female patients.
INTERPRETATION
Propranolol (80 mg) inhibits capsaicin-induced increases in dermal blood flow in a sex-dependent manner. In patients, a more pronounced decrease in triptan use is observed in males when compared with females, suggesting an interaction between propranolol and sex steroids in the modulation of the trigeminovascular system.
Topics: Adult; Capsaicin; Cross-Over Studies; Female; Humans; Male; Propranolol; Steroids; Tryptamines; Young Adult
PubMed: 36029132
DOI: 10.1002/acn3.51640 -
Plant Communications Jan 2024Plant diseases cause enormous economic losses in agriculture and threaten global food security, and application of agrochemicals is an important method of crop disease...
Plant diseases cause enormous economic losses in agriculture and threaten global food security, and application of agrochemicals is an important method of crop disease control. Exploration of disease-resistance mechanisms and synthesis of highly bioactive agrochemicals are thus important research objectives. Here, we show that propranolol, a phosphatidate phosphatase (Pah) inhibitor, effectively suppresses fungal growth, sporulation, sexual reproduction, and infection of diverse plants. The MoPah1 enzyme activity of the rice blast fungus Magnaporthe oryzae is inhibited by propranolol. Alterations in lipid metabolism are associated with inhibited hyphal growth and appressorium formation caused by propranolol in M. oryzae. Propranolol inhibits a broad spectrum of 12 plant pathogens, effectively inhibiting infection of barley, wheat, maize, tomato, and pear. To improve antifungal capacity, we synthesized a series of propranolol derivatives, one of which shows a 16-fold increase in antifungal ability and binds directly to MoPah1. Propranolol and its derivatives can also reduce the severity of rice blast and Fusarium head blight of wheat in the field. Taken together, our results demonstrate that propranolol suppresses fungal development and infection through mechanisms involved in lipid metabolism. Propranolol and its derivatives may therefore be promising candidates for fungicide development.
Topics: Fungicides, Industrial; Antifungal Agents; Oryza; Phosphatidate Phosphatase; Propranolol; Magnaporthe; Triticum
PubMed: 37653727
DOI: 10.1016/j.xplc.2023.100679 -
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 -
The Journal of Clinical Investigation Apr 2024Infantile hemangioma (IH) is a benign vascular tumor that occurs in 5% of newborns. The tumor follows a life cycle of rapid proliferation in infancy, followed by slow... (Review)
Review
Infantile hemangioma (IH) is a benign vascular tumor that occurs in 5% of newborns. The tumor follows a life cycle of rapid proliferation in infancy, followed by slow involution in childhood. This unique life cycle has attracted the interest of basic and clinical scientists alike as a paradigm for vasculogenesis, angiogenesis, and vascular regression. Unanswered questions persist about the genetic and molecular drivers of the proliferating and involuting phases. The beta blocker propranolol usually accelerates regression of problematic IHs, yet its mechanism of action on vascular proliferation and differentiation is unclear. Some IHs fail to respond to beta blockers and regrow after discontinuation. Side effects occur and long-term sequelae of propranolol treatment are unknown. This poses clinical challenges and raises novel questions about the mechanisms of vascular overgrowth in IH.
Topics: Infant, Newborn; Humans; Vascular Neoplasms; Propranolol; Disease Progression; Physicians; Hemangioma
PubMed: 38618963
DOI: 10.1172/JCI172836 -
Journal of Psychiatry & Neuroscience :... 2022Reconsolidation impairment using propranolol is a novel intervention for mental disorders with an emotional memory at their core. In this systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Reconsolidation impairment using propranolol is a novel intervention for mental disorders with an emotional memory at their core. In this systematic review and meta-analysis, we examined the evidence for this intervention in healthy and clinical adult samples.
METHODS
We searched 8 databases for randomized, double-blind studies that involved at least 1 propranolol group and 1 placebo group. We conducted a meta-analysis of 14 studies ( = 478) in healthy adults and 12 studies in clinical samples ( = 446).
RESULTS
Compared to placebo, reconsolidation impairment under propranolol resulted in reduced recall of aversive material and cue-elicited conditioned emotional responses in healthy adults, as evidenced by an effect size (Hedges ) of -0.51 ( = 0.002, 2-tailed). Moreover, compared to placebo, reconsolidation impairment under propranolol alleviated psychiatric symptoms and reduced cue-elicited reactivity in clinical samples with posttraumatic stress disorder, addiction or phobia ( = -0.42, = 0.010).
LIMITATIONS
Methodological differences between studies posed an obstacle for identifying sources of heterogeneity.
CONCLUSION
Reconsolidation impairment is a robust, well-replicated phenomenon in humans. Its clinical use is promising and deserves further controlled investigation.
Topics: Adrenergic beta-Antagonists; Adult; Emotions; Humans; Mental Recall; Propranolol; Randomized Controlled Trials as Topic
PubMed: 35361699
DOI: 10.1503/jpn.210057 -
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 -
Scientific Reports Feb 2017There is no definitive conclusion regarding the optimal timing for terminating propranolol treatment for infantile hemangioma (IH). A total of 149 patients who underwent...
There is no definitive conclusion regarding the optimal timing for terminating propranolol treatment for infantile hemangioma (IH). A total of 149 patients who underwent detailed color Doppler ultrasound examination were included in this study. The characteristics and propranolol treatment of all patients were summarized and analyzed. Patients were divided into two groups according to the lesion regression rate. Among the 149 patients, 38 were assigned to the complete regression group, and 111 were assigned to the partial regression group. The age at which propranolol treatment started, duration of follow-up after treatment discontinuation and rate of adverse events were not significantly different between the two groups. The duration of oral propranolol treatment was shorter in the complete regression group. The age at which propranolol was terminated was younger in the complete regression group, and this group had a lower recurrence rate. Propranolol is safe and effective for the treatment of IHs that require intervention, but it should be stopped at an appropriate time, which is determined primarily by the lesion regression rate after propranolol treatment. Ultrasound is helpful in determining when to stop propranolol for IH.
Topics: Administration, Oral; Antineoplastic Agents; Drug-Related Side Effects and Adverse Reactions; Female; Hemangioma; Humans; Infant; Male; Propranolol; Time Factors; Treatment Outcome
PubMed: 28225076
DOI: 10.1038/srep43292 -
British Medical Journal Jun 1969
Topics: Female; Humans; Middle Aged; Propranolol; Tinnitus
PubMed: 5786777
DOI: 10.1136/bmj.2.5659.766 -
International Journal of Molecular... Mar 2024Adrenergic pathways represent the main channel of communication between the nervous system and the immune system. During inflammation, blood monocytes migrate within...
Adrenergic pathways represent the main channel of communication between the nervous system and the immune system. During inflammation, blood monocytes migrate within tissue and differentiate into macrophages, which polarize to M1 or M2 macrophages with tissue-damaging or -reparative properties, respectively. This study investigates whether the β-adrenergic receptor (β-AR)-blocking drug propranolol modulates the monocyte-to-macrophage differentiation process and further influences macrophages in their polarization toward M1- and M2-like phenotypes. Six-day-human monocytes were cultured with M-CSF in the presence or absence of propranolol and then activated toward an M1 pro-inflammatory state or an M2 anti-inflammatory state. The chronic exposure of monocytes to propranolol during their differentiation into macrophages promoted the increase in the M1 marker CD16 and in the M2 markers CD206 and CD163 and peroxisome proliferator-activated receptor ɣ expression. It also increased endocytosis and the release of IL-10, whereas it reduced physiological reactive oxygen species. Exposure to the pro-inflammatory conditions of propranolol-differentiated macrophages resulted in an anti-inflammatory promoting effect. At the molecular level, propranolol upregulated the expression of the oxidative stress regulators NRF2, heme oxygenase-1 and NQO1. By contributing to regulating macrophage activities, propranolol may represent a novel anti-inflammatory and immunomodulating compound with relevant therapeutic potential in several inflammatory diseases.
Topics: Humans; Monocytes; Propranolol; Antioxidants; NF-E2-Related Factor 2; Macrophages; Anti-Inflammatory Agents
PubMed: 38612493
DOI: 10.3390/ijms25073683