-
British Medical Journal Feb 1973
Topics: Benzazepines; Dreams; Humans; Hypnotics and Sedatives; Nitrazepam
PubMed: 4685632
DOI: 10.1136/bmj.1.5849.353 -
American Family Physician Apr 2016
Review
Topics: Atrial Fibrillation; Benzazepines; Bradycardia; Cardiovascular Agents; Drug Costs; Heart Failure; Humans; Hypertension; Ivabradine; Treatment Outcome
PubMed: 27175841
DOI: No ID Found -
Inorganic Chemistry Jul 2022Indolo[3,2-][1]benzazepines (paullones), indolo[3,2-][2]benzazepines, and indolo[2,3-][2]benzazepines (latonduines) are isomeric scaffolds of current medicinal interest....
Elucidation of Structure-Activity Relationships in Indolobenzazepine-Derived Ligands and Their Copper(II) Complexes: the Role of Key Structural Components and Insight into the Mechanism of Action.
Indolo[3,2-][1]benzazepines (paullones), indolo[3,2-][2]benzazepines, and indolo[2,3-][2]benzazepines (latonduines) are isomeric scaffolds of current medicinal interest. Herein, we prepared a small library of novel indolo[3,2-][2]benzazepine-derived ligands - and copper(II) complexes -. All compounds were characterized by spectroscopic methods (H and C NMR, UV-vis, IR) and electrospray ionization (ESI) mass spectrometry, while complexes and , in addition, by X-ray crystallography. Their purity was confirmed by HPLC coupled with high-resolution ESI mass spectrometry and/or elemental analysis. The stability of compounds in aqueous solutions in the presence of DMSO was confirmed by H NMR and UV-vis spectroscopy measurements. The compounds revealed high antiproliferative activity in vitro in the breast cancer cell line MDA-MB-231 and hepatocellular carcinoma cell line LM3 in the low micromolar to nanomolar concentration range. Important structure-activity relationships were deduced from the comparison of anticancer activities of - and - with those of structurally similar paullone-derived (- and -) and latonduine-derived scaffolds (- and -). The high anticancer activity of the lead drug candidate was linked to reactive oxygen species and endoplasmic reticulum stress induction, which were confirmed by fluorescent microscopy and Western blot analysis.
Topics: Antineoplastic Agents; Benzazepines; Cell Line, Tumor; Coordination Complexes; Copper; Crystallography, X-Ray; Ligands; Structure-Activity Relationship
PubMed: 35713376
DOI: 10.1021/acs.inorgchem.2c01375 -
Health Technology Assessment... Sep 2009This paper presents a summary of the submission's evidence for the clinical effectiveness and cost-effectiveness of varenicline for smoking cessation included four... (Review)
Review
This paper presents a summary of the submission's evidence for the clinical effectiveness and cost-effectiveness of varenicline for smoking cessation included four studies of varenicline (one of which was commercial-in-confidence) and a meta-analysis of varenicline versus nicotine replacement therapy (NRT), bupropion and placebo. Two controlled trials of 12 weeks of varenicline versus sustained-release bupropion and placebo suggested that varenicline results in a statistically significant improvement in the odds of quitting at 12 weeks [odds ratio (OR) for quit rate during last 4 weeks of the study: 1.90-1.93 (p < 0.001) varenicline versus bupropion; 3.85 (p < 0.001) varenicline versus placebo). The ORs for sustained abstinence (weeks 9-52) for varenicline versus bupropion were 1.77 (p = 0.004) and 1.46 (p = 0.057), and for varenicline versus placebo were 2.66-3.09 (p < 0.01). A placebo-controlled maintenance trial examined whether a further 12 weeks of varenicline would maintain the rate of abstinence among those successfully treated on one 12-week course [OR = 2.48 at week 24 for varenicline versus placebo (p < 0.001)]. The meta-analysis suggested that varenicline was superior to placebo and bupropion at 1 year and 3 months. Based on indirect comparisons, varenicline was reported to be superior to NRT when compared with placebo or all controls at 1 year and 3 months. The submission presented a state transition model to estimate the incremental cost-effectiveness of varenicline compared with bupropion, NRT and placebo. The model suggests that varenicline dominates bupropion, NRT and placebo.Treatment efficacy was based on a pooled analysis of 1-year quit rates from the varenicline clinical trials. Assuming a willingness-to-pay threshold range of 20,000-30,000 pounds per quality-adjusted life-year gained, the probabilistic sensitivity analysis suggests that the probability that varenicline produces the greatest amount of net benefit is 0.70. Weaknesses of the manufacturer's submission include the assumption that only a single quit attempt using a single smoking cessation intervention is made, the presence of multiple computational errors and a limited sensitivity analysis. In conclusion, varenicline is likely to be clinically and cost-effective for smoking cessation assuming that each user makes a single quit attempt. The key area of uncertainty concerns the long-term experience of subjects who have remained abstinent from smoking beyond 12 months. The guidance issued by the National Institute for Health and Clinical Excellence in July 2007 states that varenicline is recommended within its licensed indications as an option for smokers who have expressed a desire to quit smoking and that varenicline should normally be prescribed only as part of a programme of behavioral support.
Topics: Antidepressive Agents, Second-Generation; Benzazepines; Bupropion; Clinical Trials as Topic; Cost-Benefit Analysis; Humans; Nicotinic Agonists; Quality-Adjusted Life Years; Quinoxalines; Smoking Cessation; Varenicline
PubMed: 19804684
DOI: 10.3310/hta13suppl2/02 -
British Medical Journal Jul 1969In 27 patients nitrazepam (Mogadon) taken in acute overdosage produced no untoward effects except drowsiness, even when 80 tablets were consumed. A double-blind trial in... (Clinical Trial)
Clinical Trial Comparative Study
In 27 patients nitrazepam (Mogadon) taken in acute overdosage produced no untoward effects except drowsiness, even when 80 tablets were consumed. A double-blind trial in patients in general medical wards established that nitrazepam was as effective as butobarbitone as a hypnotic. It is concluded that nitrazepam is a safe and effective hypnotic.
Topics: Adult; Aged; Barbiturates; Benzazepines; Clinical Trials as Topic; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Placebos; Sleep; Sleep Initiation and Maintenance Disorders; Time Factors
PubMed: 4892037
DOI: 10.1136/bmj.3.5661.23 -
Cardiovascular Therapeutics Aug 2014Results of recent clinical trials in patients with stable angina and chronic heart failure have successfully demonstrated a beneficial role of use of ivabradine in... (Review)
Review
Results of recent clinical trials in patients with stable angina and chronic heart failure have successfully demonstrated a beneficial role of use of ivabradine in addition to the conventional therapy. Based on the results of these trials, the aim of our review was to give an overview of the literature about the use of ivabradine in clinical settings outside its usual purpose.
Topics: Anti-Arrhythmia Agents; Benzazepines; Heart Diseases; Humans; Ivabradine; Pulmonary Disease, Chronic Obstructive; Treatment Outcome
PubMed: 24828443
DOI: 10.1111/1755-5922.12080 -
American Journal of Cardiovascular... Apr 2016We reviewed clinical evidence for the use of ivabradine in systolic heart failure (HF), in which it appears to improve symptoms, improve quality of life, prevent... (Review)
Review
We reviewed clinical evidence for the use of ivabradine in systolic heart failure (HF), in which it appears to improve symptoms, improve quality of life, prevent hospitalization, and prolong survival, thereby addressing unmet needs in the management of HF. Ivabradine provides symptomatic benefits in HF on top of standard therapies, in terms of functional parameters and exercise capacity, and there is some evidence that this leads to improvements in quality of life in symptomatic HF patients, who may have dyspnea, altered exercise capacity, and fatigue. The SHIFT trial demonstrated that ivabradine has significant beneficial effects on major outcomes in HF. Ivabradine had a significant effect on pump failure death, which was reduced by 26 % (p = 0.014), with no effect on sudden cardiac death. This is an important result since pump failure death is currently the main cause of death in HF, and also because the reductions in mortality obtained with beta-blockers and spironolactone in the last 20 years appear to be mainly due to reduction in sudden death rather than reduction in pump failure death. Ivabradine also has a beneficial effect on hospital admissions (-26 %, p < 0.0001), which is clinically relevant since a quarter of HF patients can expect to be readmitted to hospital for HF within 1 month of discharge. Ivabradine-treated patients are also at significantly lower risk of experiencing a second or third hospitalization for worsening HF. Ivabradine clearly has a key role to play in the management of HF by covering the main therapeutic objectives of symptoms, quality of life, and outcomes.
Topics: Benzazepines; Cardiovascular Agents; Heart Failure, Systolic; Hospitalization; Humans; Ivabradine; Quality of Life; Treatment Outcome
PubMed: 26817946
DOI: 10.1007/s40256-016-0159-2 -
Therapeutic Advances in Cardiovascular... 2021For decades, plasma arginine vasopressin (AVP) levels have been known to be elevated in patients with congestive heart failure (HF). Excessive AVP signaling at either or... (Review)
Review
For decades, plasma arginine vasopressin (AVP) levels have been known to be elevated in patients with congestive heart failure (HF). Excessive AVP signaling at either or both the V1a and V2 receptors could contribute to the pathophysiology of HF by several mechanisms. V1a activation could cause vasoconstriction and/or direct myocardial hypertrophy as intracellular signaling pathways are closely related to those for angiotensin II. V2 activation could cause fluid retention and hyponatremia. A hemodynamic study with the pure V2 antagonist tolvaptan (TV) showed minimal hemodynamic effects. Compared with furosemide in another study, the renal and neurohormonal effects of TV were favorable. Several clinical trials with TV as adjunctive therapy in acute HF have shown beneficial effects on fluid balance and dyspnea, with no worsening of renal function or neurohormonal stimulation. Two smaller studies, one in acute and one in chronic HF, have shown comparable clinical and more favorable renal and neurohormonal effects of TV compared with loop diuretics. However, long-term treatment with TV did not alter outcomes in acute HF. No data are available other than single-dose studies of an intravenous pure V1a antagonist, which showed a vasodilating effect if plasma AVP levels were elevated. One hemodynamic study and one short-duration clinical trial with the balanced intravenous V1a/V2 antagonist conivaptan (CV) showed hemodynamic and clinical effects largely similar to those with TV in similar studies. A new orally effective balanced V1/V2 antagonist (pecavaptan) is currently undergoing phase II study as both adjunctive and alternative therapy during and after hospitalization for acute HF. The purpose of this review is to summarize what we have learned from the clinical experience with TV and CV, and to suggest implications of these findings for future work with newer agents.
Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Clinical Trials as Topic; Heart Failure; Hemodynamics; Humans; Receptors, Vasopressin; Signal Transduction; Tolvaptan; Treatment Outcome
PubMed: 33435837
DOI: 10.1177/1753944720977741 -
CNS Drug Reviews 2001SCH 23390, the halobenzazepine (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5- tetrahydro-1H-3-benzazepine, is a highly potent and selective dopamine D1-like... (Review)
Review
SCH 23390, the halobenzazepine (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5- tetrahydro-1H-3-benzazepine, is a highly potent and selective dopamine D1-like receptor antagonist with a K(i) of 0.2 and 0.3 nM for the D1 and D5 dopamine receptor subtypes, respectively. In vitro, it also binds with high affinity to the 5-HT2 and 5-HT1C serotonin receptor subtypes. However, the doses required to induce a similar response in vivo are greater than 10-fold higher than those required to induce a D1-mediated response. Previous in vivo pharmacological studies with SCH 23390 have shown it to abolish generalized seizures evoked by the chemoconvulsants: pilocarpine and soman. These studies provide evidence of the potential importance of D1-like dopaminergic receptor mechanisms in facilitating the initiation and spread of seizures. The inference from a majority of studies is that the activation of dopamine D1 receptors facilitates seizure activity, whereas activation of D2 receptors may inhibit the development of seizures. SCH 23390 has also been used in studies of other neurological disorders in which the dopamine system has been implicated, such as psychosis and Parkinson's disease. Apart from the study of neurological disorders, SCH 23390 has been extensively used as a tool in the topographical determination of brain D1 receptors in rodents, nonhuman primates, and humans. In summary, SCH 23390 has been a major tool in gaining a better understanding of the role of the dopamine system, more specifically the D1 receptor, in neurological function and dysfunction.
Topics: Animals; Anticonvulsants; Antipsychotic Agents; Behavior, Animal; Benzazepines; Brain; Dopamine; Dopamine Antagonists; Electroencephalography; Humans; Huntington Disease; Memory; Motor Activity; Parkinson Disease; Psychotic Disorders; Receptors, Dopamine D1; Receptors, Dopamine D5; Seizures; gamma-Aminobutyric Acid
PubMed: 11830757
DOI: 10.1111/j.1527-3458.2001.tb00207.x -
Drugs Sep 2013Heart rate is an important contributor in the pathophysiology of both coronary artery disease (CAD) and heart failure (HF). Ivabradine is an anti-anginal and... (Review)
Review
Heart rate is an important contributor in the pathophysiology of both coronary artery disease (CAD) and heart failure (HF). Ivabradine is an anti-anginal and anti-ischaemic agent, which selectively and specifically inhibits the I f current in the sino-atrial node and provides pure heart rate reduction without altering other cardiac parameters, including conduction, and without directly affecting other haemodynamic parameters. It is approved for the treatment of CAD and HF. This article summarises the pharmacological properties, pharmacokinetics, clinical efficacy and tolerability of ivabradine in the treatment of CAD and HF, and presents evidence demonstrating that the pharmacological and clinical properties and clinical efficacy of ivabradine make it an important therapeutic choice for patients with stable CAD or HF. The positive effect of ivabradine on angina pectoris symptoms and its ability to reduce myocardial ischemia make it an important agent in the management of patients with stable CAD or chronic HF. Further studies are underway to add to the already robust evidence of ivabradine for the prevention of cardiovascular events in patients with CAD but without clinical HF. The SIGNIFY (Study assessInG the morbidity-mortality beNefits of the I f inhibitor ivabradine in patients with coronarY artery disease) trial includes patients with stable CAD and an LVEF above 40 %, with no clinical sign of HF, and is investigating the long-term effects (over a period of 48 months) of ivabradine in a large study population. So far, this study has included more than 19,000 patients from 51 countries.
Topics: Animals; Benzazepines; Cardiovascular Agents; Coronary Artery Disease; Heart Failure; Heart Rate; Humans; Ivabradine
PubMed: 24065301
DOI: 10.1007/s40265-013-0117-0