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Anesthesia and Analgesia Aug 2007
Topics: Cardiopulmonary Bypass; Humans; Hypoplastic Left Heart Syndrome; Phenoxybenzamine
PubMed: 17646480
DOI: 10.1213/01.ane.0000271915.56275.0c -
PloS One 2018The principal finding from this study was the recognition that the α-adrenergic antagonist, phenoxybenzamine, possesses histone deacetylase inhibitory activity....
The principal finding from this study was the recognition that the α-adrenergic antagonist, phenoxybenzamine, possesses histone deacetylase inhibitory activity. Phenoxybenzamine is approved by the United States Food and Drug Administration for the treatment of hypertensive crises associated with tumors of the adrenal medulla, pheochromocytomas. It has several "off label" indications relative to its capacity to relax vascular smooth muscle and smooth muscle of the urogenital tract. The drug also has a long history of apparent efficacy in ameliorating, and perhaps reversing, the severe symptoms of neuropathic pain syndromes. Our interest in this feature of the drug relates to the fact that certain types of neuropathic pain, in particular complex regional pain syndrome, demonstrate a proliferative nature, with the capacity to spread from an injured limb, for example, to a non-injured limb and perhaps to essentially the entire body. Sensory neuronal sprouting in the spinal cord has been observed under conditions where there is a high sensory input from painful stimuli. Searches of gene expression signatures in the BroadBuild02 Molecular Signature Database using their connectivity map software suggested that phenoxybenzamine may have histone deacetylase inhibitory activity. Studies by others have reported inhibitory effects of phenoxybenzamine on growth, invasion and migration of human tumor cell cultures and, in one study, inhibition of tumor expansion in animal experiments. Inhibitory effects on human tumor cell cultures are also reported in the present study. Phenoxybenzamine was also found to have histone deacetylase inhibitory activity; histone deacetylase isoforms 5, 6, and 9 were the most sensitive to inhibition by phenoxybenzamine. The importance of elevated levels of these isoforms as biomarkers of poor prognosis in human malignant disease, and the recognized suppression of tumor growth that may accrue from their inhibition, opens consideration of possible translation of phenoxybenzamine to new clinical applications. This might be facilitated by the fact that phenoxybenzamine is already an approved drug entity. There appears to be no previous report of the activity of phenoxybenzamine as a histone deacetylase inhibitor.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Databases, Factual; Histone Deacetylases; Humans; Inhibitory Concentration 50; Isoenzymes; Neoplasms; Phenoxybenzamine
PubMed: 29897996
DOI: 10.1371/journal.pone.0198514 -
Report on Carcinogens : Carcinogen... 2004
Topics: Animals; Antihypertensive Agents; Carcinogenicity Tests; Carcinogens; Female; Government Regulation; Guidelines as Topic; Humans; Male; Mice; Models, Biological; Occupational Exposure; Phenoxybenzamine; Rats; United States
PubMed: 21089945
DOI: No ID Found -
Report on Carcinogens : Carcinogen... 2002
Topics: Animals; Carcinogens; Environmental Exposure; Government Regulation; Humans; Phenoxybenzamine; United States
PubMed: 15332291
DOI: No ID Found -
Interactive Cardiovascular and Thoracic... Oct 2008Phenoxybenzamine, an irreversible alpha-adrenoceptor antagonist, is used as a topical treatment against catecholamine-induced contraction in radial artery bypass grafts....
Phenoxybenzamine, an irreversible alpha-adrenoceptor antagonist, is used as a topical treatment against catecholamine-induced contraction in radial artery bypass grafts. Published data suggest that a wide range of phenoxybenzamine doses may be equally effective. This study aimed to investigate whether lower doses of phenoxybenzamine would benefit grafts by better preserving endothelium. To this end human vascular endothelial cells were isolated from sections of radial artery or saphenous vein, and treated with phenoxybenzamine for 30 min. Cells were then washed free of drug and viability assayed using a resazurin-based toxicology assay or returned to culture for assay at 24 h. Phenoxybenzamine treatment showed a dose-dependent effect on cell viability over several clinically employed concentrations. Concentrations above 0.1 mM led to a loss of viability, which became more pronounced with time. The loss of viability was shown to be independent of the carrier used, as results were identical when phenoxybenzamine was dissolved in dimethylsulphoxide, which alone did not affect viability. Changes in pH alone were also not sufficient to affect viability. In conclusion, phenoxybenzamine treatment is likely to cause damage to graft endothelium if employed at concentrations above 0.1 mM (0.03 mg/ml). Phenoxybenzamine may be safely used at lower doses with no potential loss of endothelial cell viability.
Topics: Adrenergic alpha-Antagonists; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Endothelial Cells; Humans; Phenoxybenzamine; Time Factors
PubMed: 18573847
DOI: 10.1510/icvts.2008.175281 -
Clinical Therapeutics Jun 2002Phenoxybenzamine (PBZ) is a nonselective, irreversible alpha-adrenergic receptor antagonist that is approved for the treatment of diaphoresis and hypertension associated... (Review)
Review
BACKGROUND
Phenoxybenzamine (PBZ) is a nonselective, irreversible alpha-adrenergic receptor antagonist that is approved for the treatment of diaphoresis and hypertension associated with pheochromocytoma. It may also be useful in several chronic conditions whose pathogenesis is mediated or affected by alpha-adrenergic stimulation, such as lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH) and neurogenic bladder (eg, secondary to myelomeningocele and in sphincter dyssynergia and autonomic dysreflexia); in an adjunctive role after urogenital surgery or brachytherapy by relieving symptoms associated with increased alpha-adrenergic tone; and in the treatment of complex regional pain syndrome (CRPS) and prostatitis. However, carcinogenic concerns may have limited its potential application.
OBJECTIVE
The purpose of this article is to reassess the usefulness and contemporary application of PBZ for the control of urinary tract symptoms associated with BPH and neurogenic bladder, after urogenital surgery and brachytherapy, and in certain other conditions (eg, CRPS, prostatitis).
METHODS
A search of literature published from 1966 to 2002 was performed on MEDLINE using the search terms phenoxybenzamine, alpha-adrenergic blockers, benign prostatic hyperplasia, neurogenic bladder, urinary retention, and complex regional pain
RESULTS
Despite concerns about possible carcinogenicity, no reports of drug-related tumors have been made since PBZ's introduction in 1953. Investigators have used PBZ in off-label trials to alleviate symptoms of a variety of conditions that cause urinary retention. In adult male patients with retention due to inguinal hernioplasty and female patients with retention caused by vaginal repair, as well as in pediatric patients with myelomeningocele, treatment with PBZ improved bladder function and, in the patients with myelomeningocele, was associated with reduced incidence of urinary tract infection. Larger tri- als of PBZ in men with BPH produced significant urinary symptom relief (P < 0.05 in 2 studies). Moreover, studies suggest that PBZ may be useful in alleviating pain due to trauma and CRPS. The most common adverse events appear to be dizziness, impotence and ejaculatory dysfunction, and nasal stuffiness.
CONCLUSIONS
No drug-related tumors in humans have been reported after -50 years of clinical experience with PBZ. Clinical trials have demonstrated that it can relieve symptoms in patients with BPH and other urologic and pain-related conditions.
Topics: Adrenergic alpha-Antagonists; Animals; Clinical Trials as Topic; Half-Life; Humans; Male; Phenoxybenzamine; Prostatic Hyperplasia; Rats; Tissue Distribution; Urinary Tract Infections
PubMed: 12117078
DOI: 10.1016/s0149-2918(02)80003-0 -
Comprehensive Therapy Jun 1979
Topics: Aged; Humans; Male; Middle Aged; Phenoxybenzamine; Prostatic Hyperplasia
PubMed: 88294
DOI: No ID Found -
Kardiologia Polska 2017Adrenalectomy with preoperative pharmacological preparation is strongly recommended in patients diagnosed with pheochromocytoma, in order to prevent perioperative... (Comparative Study)
Comparative Study
BACKGROUND
Adrenalectomy with preoperative pharmacological preparation is strongly recommended in patients diagnosed with pheochromocytoma, in order to prevent perioperative complications.
AIM
To compare phenoxybenzamine (PhB) and doxazosin (DOX) in terms of perioperative haemodynamic status in patients with pheochromocytoma, who have been prepared for adrenalectomy.
METHODS
Retrospective analysis of 44 patients with pheochromocytoma (aged 16-80 years, 29 females) who underwent adrenalectomy. Patients were divided into two groups: 35 patients on DOX and nine patients on PhB.
RESULTS
Mean time of preparation for surgery was 38.8 days in the DOX group and 18.3 days in the PhB group (p = 0.04). No statistically significant differences between the DOX and PhB groups in intraoperative blood pressure (BP) fluctuations were found: < 170/100 mm Hg (34% vs. 44%, respectively, p = 0.42), ≥ 200/110 mm Hg (40% vs. 22%, respectively, p = 0.28). Mean greatest intraoperative systolic BP (195 ± 53 vs. 166 ± 42 mm Hg, p = 0.21) and diastolic BP (98 ± 20 vs. 89 ± 46 mm Hg, p = 0.21), and mean lowest intraoperative systolic BP (87 ± 13 vs. 79 ± 17 mm Hg, p = 0.25) and diastolic BP (49 ± 8 vs. 46 ± 12 mm Hg, p = 0.60) were not different between the DOX and PhB groups, respectively. Sodium nitroprusside was administrated in 30% DOX vs. 11% PhB patients (p = 0.25). Laparoscopic surgery was conducted in 97% DOX vs. 89% PhB patients (p = 0.64). Postoperative BP drop below 90/60 mm Hg was noted in 48% of the DOX vs. 43% of the PhB group (p = 0.56). Negative correlation was found between the length of DOX administration with maximal intraoperative systolic BP (r = -0.45, p = 0.006) and diastolic BP (r = -0.39, p = 0.019).
CONCLUSIONS
There are no clinically relevant differences between patients with pheochromocytoma, who have been prepared for adrenalectomy with DOX or PhB.
Topics: Adrenalectomy; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Disease Management; Doxazosin; Female; Humans; Male; Middle Aged; Phenoxybenzamine; Pheochromocytoma; Postoperative Complications; Prohibitins; Retrospective Studies; Young Adult
PubMed: 28715066
DOI: 10.5603/KP.a2017.0147 -
JAMA Dec 1970
Topics: Adrenergic alpha-Antagonists; Humans; Phenoxybenzamine; Phentolamine; Reflex, Abnormal; Sympatholytics
PubMed: 4396220
DOI: 10.1001/jama.214.10.1886c -
British Journal of Urology Jan 1987Forty-five patients awaiting prostatectomy participated in a double-blind study of phenoxybenzamine 10 mg/day for 5 weeks. Objective measurements of peak urine flow,... (Clinical Trial)
Clinical Trial
Forty-five patients awaiting prostatectomy participated in a double-blind study of phenoxybenzamine 10 mg/day for 5 weeks. Objective measurements of peak urine flow, voided volume, residual urine and frequency of micturition and nocturia showed no significant difference between phenoxybenzamine and placebo. Patients taking phenoxybenzamine had a significantly greater improvement in hesitancy and flow symptoms than those on placebo. Side effects occurred in 47.6% of patients on phenoxybenzamine and 22.2% of those on placebo. In this study phenoxybenzamine 10 mg/day was ineffective in patients with benign prostatic hypertrophy.
Topics: Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Humans; Male; Middle Aged; Phenoxybenzamine; Prostatic Hyperplasia; Random Allocation
PubMed: 2435356
DOI: 10.1111/j.1464-410x.1987.tb04581.x