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Chemical Science Sep 2021A general approach to a new generation of spirocyclic molecules - oxa-spirocycles - was developed. The key synthetic step was iodocyclization. More than 150...
A general approach to a new generation of spirocyclic molecules - oxa-spirocycles - was developed. The key synthetic step was iodocyclization. More than 150 oxa-spirocyclic compounds were prepared. Incorporation of an oxygen atom into the spirocyclic unit dramatically improved water solubility (by up to 40 times) and lowered lipophilicity. More potent oxa-spirocyclic analogues of antihypertensive drug terazosin were synthesized and studied .
PubMed: 34667540
DOI: 10.1039/d1sc03615g -
Pakistan Journal of Medical Sciences 2022To study the therapeutic effects of combined tamsulosin hydrochloride and terazosin treatment for patients with chronic prostatitis Type-III b.
OBJECTIVES
To study the therapeutic effects of combined tamsulosin hydrochloride and terazosin treatment for patients with chronic prostatitis Type-III b.
METHODS
This study involved 180 patients with chronic prostatitis Type-III b treated between January 2018 and December 2020 conducted at Nanhua Hospital Affiliated to Nanhua University. Patients were randomly divided into two equal groups: one receiving oral terazosin hydrochloride tablets only (control group), and one orally receiving both tamsulosin hydrochloride sustained-release tablets and terazosin hydrochloride tablets (observation group). Outcome measurements included symptom scoring, inflammatory cytokine levels, as well as white blood cell and lecithin body counts in the prostatic fluid.
RESULTS
After 30 days of treatment, the observation group showed greater treatment effectiveness (86.67% vs. 73.33%, P<0.05). QLS, USS, PS, and NIH-CPSI symptom scores were lower in the observation group than the control group (P<0.05). No differences in adverse event distribution and incidence were noted. EPS IL-2 increased more in the observation group, while PGE-2, MIP-1α, and MIP-2 decreased more in the observation group. WBC levels decreased more in the observation group, while lecithin body levels increased more in the observation group.
CONCLUSION
The combination of tamsulosin hydrochloride and terazosin for the treatment of patients with chronic prostatitis Type-III b has a significant effect. This approach reduced patient symptoms, lowered inflammatory biomarkers, and generally improved quality of life. This approach appears to have clinical value worthy of future investigation.
PubMed: 35480502
DOI: 10.12669/pjms.38.3.4931 -
Archivos Espanoles de Urologia Oct 2023This study aimed to explore the effect of terazosin hydrochloride combined with interventional embolisation on prostate volume and quality of life (QOL) of elderly...
OBJECTIVE
This study aimed to explore the effect of terazosin hydrochloride combined with interventional embolisation on prostate volume and quality of life (QOL) of elderly patients with prostatic hyperplasia (PH).
METHODS
The clinical data of 175 elderly patients with PH admitted to Central Hospital Affiliated to Shandong First Medical University from July 2020 to July 2022 were selected for retrospective analysis. Based on different treatment regimens, 89 patients who received interventional embolisation alone were included in the control group (CG), and 86 patients undergoing interventional embolisation combined with terazosin hydrochloride were included in the study group (SG). The prostate volume, serum indicators, adverse reactions and QOL of the two groups before and after treatment were compared between the two groups.
RESULTS
Before treatment, no significant difference in 36-item short-form health survey (SF-36) scores, serum tumour necrosis factor-α (TNF-α) and prostate-specific antigen (PSA) was observed in both groups ( > 0.05). After treatment, the SF-36 score in the SG was 78.20 ± 6.84 points, which was significantly higher than that in the CG (72.67 ± 5.94 points). In addition, the SG had remarkably lower residual urine volume and prostate volume, higher maximum flow rate and lower TNF-α and PSA levels compared with the CG ( < 0.05). The adverse reaction rate of the SG was only 4.65%, which was significantly lower than that of the CG (14.61%, < 0.05).
CONCLUSIONS
Terazosin hydrochloride combined with interventional embolisation overtly reduces the prostate volume and improves the clinical symptoms of patients with fewer side effects, which has a certain clinical application value.
Topics: Aged; Humans; Male; Adrenergic alpha-Antagonists; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Quality of Life; Retrospective Studies; Treatment Outcome; Tumor Necrosis Factor-alpha; Embolization, Therapeutic; Urological Agents
PubMed: 37960955
DOI: 10.56434/j.arch.esp.urol.20237608.70 -
Central European Journal of Urology 2013The α1-adrenoreceptor antagonists, such as terazosin and doxazosin, induce prostate programmed cell death (apoptosis) within prostate epithelial and stromal cells in... (Review)
Review
PURPOSE
The α1-adrenoreceptor antagonists, such as terazosin and doxazosin, induce prostate programmed cell death (apoptosis) within prostate epithelial and stromal cells in vitro. This treatment should cause prostate volume decrease, However, this has never been observed in clinical conditions. The aim of this paper is to review the disconnect between these two processes.
METHODS
PubMed and DOAJ were searched for papers related to prostate, apoptosis, and stem cell death. The following key words were used: prostate, benign prostate hyperplasia, programmed cell death, apoptosis, cell death, α1-adrenoreceptor antagonist, α-blockade, prostate epithelium, prostate stroma, stem cells, progenitors, and in vitro models.
RESULTS
We have shown how discoveries related to stem cells can influence our understanding of α-blockade treatment for BPH patients. Prostate epithelial and mesenchymal compartments have stem (progenitors) and differentiating cells. These compartments are described in relation to experimental in vitro and in vivo settings.
CONCLUSIONS
Apoptosis is observed within prostate tissue, but this effect has no clinical significance and cannot lead to prostate shrinkage. In part, this is due to stem cells that are responsible for prostate tissue regeneration and are resistant to apoptosis triggered by α1-receptor antagonists.
PubMed: 24579025
DOI: 10.5173/ceju.2013.02.art19 -
European Journal of Hospital Pharmacy :... Jul 2022Surgery is the primary strategy for treating phaeochromocytoma (PCC), but it can lead to severe hypertension and heart failure. Although valsartan is effective in...
OBJECTIVE
Surgery is the primary strategy for treating phaeochromocytoma (PCC), but it can lead to severe hypertension and heart failure. Although valsartan is effective in reducing high blood pressure, clinical data on the potential role of valsartan in PCC are currently limited. Therefore, the aim of this study was to investigate the effects of pretreatment with terazosin and valsartan on patients with PCC.
METHODS
In this retrospective cohort study, 50 patients who underwent laparoscopic resection of PCC were enrolled. During preoperative preparation, the patients (n=25) in the control group were treated with terazosin, while those (n=25) in the combination treatment group were treated with terazosin and valsartan. The levels of catecholamine hormones before and after surgery were determined, and the intraoperative blood pressure and the incidence of complications were compared between the two groups.
RESULTS
The results showed no significant differences in baseline patient characteristics or surgical conditions between the two groups (p>0.05). However, on the third day after surgery, the levels of catecholamine hormones in the two groups were significantly lower than those before surgery (p<0.05), while the levels in the combination treatment group were notably lower than those in the control group (p<0.05). The patients in the combination treatment group showed lower intraoperative blood pressure fluctuations and incidence of perioperative complications compared with the control group (p<0.05).
CONCLUSIONS
Terazosin combined with valsartan can effectively improve perioperative haemodynamic instability and reduce postoperative complications in the preoperative management of PCC.
Topics: Adrenal Gland Neoplasms; Catecholamines; Hemodynamics; Hormones; Humans; Pheochromocytoma; Prazosin; Retrospective Studies; Valsartan
PubMed: 32895230
DOI: 10.1136/ejhpharm-2020-002375 -
The Cochrane Database of Systematic... Sep 2011Lower urinary tract symptoms associated with benign prostatic obstruction (BPO) occur in up to 70% of men over the age of 60 years. To relieve these bothersome symptoms,... (Review)
Review
BACKGROUND
Lower urinary tract symptoms associated with benign prostatic obstruction (BPO) occur in up to 70% of men over the age of 60 years. To relieve these bothersome symptoms, treatment options include alpha-antagonists, also know as alpha-blockers.
OBJECTIVES
We conducted a systematic review to evaluate the effectiveness and adverse effects of the alpha-blocker, terazosin, for treatment of urinary symptoms associated with BPO.
SEARCH STRATEGY
Trials were searched in computerized general and specialized databases (MEDLINE, Cochrane Library), by checking bibliographies, and by contacting manufacturers and researchers.
SELECTION CRITERIA
Studies were included if they (1) were randomized trials of at least 1 month duration, and (2) included men with symptomatic BPO and compared terazosin with placebo or active controls.
DATA COLLECTION AND ANALYSIS
Study, patient characteristics and outcomes data were extracted in duplicate onto standardized forms utilizing a prospectively developed protocol. The main outcome measure for comparing the effectiveness of terazosin with placebo or other BPO medications was change in urological symptoms as measured by validated symptom scores. Secondary outcomes included urodynamic measures. The main outcome measure for adverse effects was the number of men reporting side effects. We also evaluated the number of men withdrawing from treatment and the number withdrawing due to adverse effects.
MAIN RESULTS
Seventeen studies involving 5151 subjects met inclusion criteria (placebo-controlled (n = 10); alpha-blockers (n = 7); finasteride alone or in combination with terazosin as well as placebo (1); microwave therapy (TUMT) (1). Study duration ranged from 4 to 52 weeks. Mean age was 65 years and 82% of men were white. Baseline urologic symptom scale scores and flow rates demonstrated that men had moderate BPO. Efficacy outcomes were rarely reported in a fashion that allowed for data pooling but indicated that terazosin improved symptom scores and flow rates more than placebo or finasteride and similarly to other alpha antagonists. The pooled mean percentage improvements for the Boyarsky symptom score was 37% for terazosin versus 15% for placebo (n = 4 studies). The mean percentage improvement for the American Urological Association symptom score (AUA) was 38% compared to 17% and 20% for placebo and finasteride, respectively (n = 2 studies). The pooled mean improvement in the International Prostate Symptom Score (IPSS) (40%) was similar to tamsulosin (43%). Peak urine flow rates improved greater with terazosin (22%), than placebo (11%) and finasteride (15%) but did not differ significantly from the other alpha-blockers. The percentage of men discontinuing terazosin was comparable to men receiving placebo and finasteride but was greater then with other alpha-antagonists. Adverse effects were greater than placebo and included dizziness, asthenia, headache, and postural hypotension.
AUTHORS' CONCLUSIONS
The available evidence suggests that terazosin improves urinary symptoms and flow measures associated with BPO. Effectiveness is superior to placebo or finasteride, similar to other alpha-blockers but less than TUMT. Adverse effects were generally mild but more frequent than other alpha-blockers and associated with between a two-to-four fold increase in treatment discontinuation.
Topics: Adrenergic alpha-Antagonists; Aged; Antineoplastic Agents; Humans; Male; Middle Aged; Prazosin; Prostatic Hyperplasia
PubMed: 21901686
DOI: 10.1002/14651858.CD003851.pub2 -
Antibiotics (Basel, Switzerland) Mar 2022is an invasive intracellular pathogen and hires diverse systems to manipulate its survival in the host cells. could eavesdrop on the host cells, sensing and responding...
is an invasive intracellular pathogen and hires diverse systems to manipulate its survival in the host cells. could eavesdrop on the host cells, sensing and responding to the produced adrenergic hormones and other neurotransmitters, which results in the augmentation of its virulence and establishes its accommodation in host cells. The current study aims to assess the anti-virulence effect of α-adrenergic antagonist terazosin on Typhimurium. Our findings show that terazosin significantly reduced Typhimurium adhesion and biofilm formation. Furthermore, terazosin significantly decreased invasion and intracellular replication of Typhimurium. Interestingly, in vivo, terazosin protected the mice from Typhimurium pathogenesis. To understand the terazosin anti-virulence activity, its effect on quorum sensing (QS), bacterial espionage, and type three secretion system (T3SS) was studied. Strikingly, terazosin competed on the membranal sensors that sense adrenergic hormones and down-regulated their encoding genes, which indicates the ability of terazosin to diminish the bacterial eavesdropping on the host cells. Moreover, terazosin significantly reduced the QS-controlled pigment production and interfered with the QS receptor Lux-homolog SdiA, which indicates the possible terazosin-mediated anti-QS activity. Furthermore, terazosin down-regulated the expression of T3SS encoding genes. In conclusion, terazosin may mitigate Typhimurium virulence owing to its hindering QS and down-regulating T3SS encoding genes besides its inhibition of bacterial espionage.
PubMed: 35453216
DOI: 10.3390/antibiotics11040465 -
EBioMedicine Sep 2022Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with heterogeneous aetiology and a complex genetic background. Effective therapies are...
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with heterogeneous aetiology and a complex genetic background. Effective therapies are therefore likely to act on convergent pathways such as dysregulated energy metabolism, linked to multiple neurodegenerative diseases including ALS.
METHODS
Activity of the glycolysis enzyme phosphoglycerate kinase 1 (PGK1) was increased genetically or pharmacologically using terazosin in zebrafish, mouse and ESC-derived motor neuron models of ALS. Multiple disease phenotypes were assessed to determine the therapeutic potential of this approach, including axon growth and motor behaviour, survival and cell death following oxidative stress.
FINDINGS
We have found that targeting a single bioenergetic protein, PGK1, modulates motor neuron vulnerability in vivo. In zebrafish models of ALS, overexpression of PGK1 rescued motor axon phenotypes and improved motor behaviour. Treatment with terazosin, an FDA-approved compound with a known non-canonical action of increasing PGK1 activity, also improved these phenotypes. Terazosin treatment extended survival, improved motor phenotypes and increased motor neuron number in Thy1-hTDP-43 mice. In ESC-derived motor neurons expressing TDP-43, terazosin protected against oxidative stress-induced cell death and increased basal glycolysis rates, while rescuing stress granule assembly.
INTERPRETATION
Our data demonstrate that terazosin protects motor neurons via multiple pathways, including upregulating glycolysis and rescuing stress granule formation. Repurposing terazosin therefore has the potential to increase the limited therapeutic options across all forms of ALS, irrespective of disease cause.
FUNDING
This work was supported by project grant funding from MND Scotland, the My Name'5 Doddie Foundation, Medical Research Council Doctoral Student Training Fellowship [Ref: BST0010Z] and Academy of Medical Sciences grant [SGL023\1100].
Topics: Amyotrophic Lateral Sclerosis; Animals; DNA-Binding Proteins; Humans; Mice; Motor Neurons; Phenotype; Phosphoglycerate Kinase; Prazosin; Zebrafish
PubMed: 35963713
DOI: 10.1016/j.ebiom.2022.104202 -
International Journal of Molecular... Dec 2021Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them,...
Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.
Topics: Apoptosis; Caco-2 Cells; Cell Survival; Colitis; Cytokines; Deoxyglucose; Dextran Sulfate; Gastric Mucosa; Gastrointestinal Diseases; Glucose; Humans; Hydrogen Peroxide; Inflammation Mediators; Lactic Acid; Malondialdehyde; Models, Biological; Peroxidase; Phosphoglycerate Kinase; Prazosin; Pyroptosis; Stomach Ulcer; Superoxide Dismutase
PubMed: 35008842
DOI: 10.3390/ijms23010416 -
Expert Opinion on Therapeutic Targets Dec 2011Mechanistic, translational and pharmacological studies led to the identification and discovery of the preferred localization, binding characteristics, structure and... (Review)
Review
INTRODUCTION
Mechanistic, translational and pharmacological studies led to the identification and discovery of the preferred localization, binding characteristics, structure and functional properties of α1-adrenoceptor (α1-AR) subtypes in the bladder neck, bladder and prostate gland. The evidence gathered on α1-ARs, provided a molecular platform for the development of subtype-selective antagonists, resulting in more effective approaches targeting those receptors for the treatment of outlet bladder obstruction and benign prostate hyperplasia.
AREAS COVERED
Advances over the last decade in the design and optimization of Prazosin, Doxazosin and Terazosin quinazoline-based derivatives as α1-AR antagonists. Evidence on the metabolic and growth interference action by these agents, in addition to their smooth-muscle-relaxing effects. The new action recognition emerges from data on the inhibitory effect of quinazoline-based antagonists on primary tumor growth and progression to metastasis. In addition to the cellular findings in the prostate, functional validation and therapeutic effects of selected lead pharmaceutically optimized derivatives in the context of impairing vascularity and triggering tumor apoptosis.
EXPERT OPINION
Knowledge on targeting intracellular signalling pathways driving the cellular response via an α1-AR-dependent and independent antagonistic action, must be invested towards the optimization of new agents that while bypassing AR, exhibit improved pharmacological efficacy against human cancer.
Topics: Adrenergic alpha-1 Receptor Antagonists; Antihypertensive Agents; Drug Design; Humans; Hypertension; Male; Prazosin; Prostatic Hyperplasia; Receptors, Adrenergic; Receptors, Adrenergic, alpha-1; Urinary Bladder Neck Obstruction
PubMed: 22148952
DOI: 10.1517/14728222.2011.641534