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The Alkaloids. Chemistry and Biology 2017Cephalotaxus alkaloids represent a family of plant secondary metabolites known for 60 years. Significant activity against leukemia in mice was demonstrated for extracts... (Review)
Review
Cephalotaxus alkaloids represent a family of plant secondary metabolites known for 60 years. Significant activity against leukemia in mice was demonstrated for extracts of Cephalotaxus. Cephalotaxine (CET) (1), the major alkaloid of this series was isolated from Cephalotaxus drupacea species by Paudler in 1963. The subsequent discovery of promising antitumor activity among new Cephalotaxus derivatives reported by Chinese, Japanese, and American teams triggered extensive structure elucidation and biological studies in this family. The structural feature of this cephalotaxane family relies mainly on its tetracyclic alkaloid backbone, which comprises an azaspiranic 1-azaspiro[4.4]nonane unit (rings C and D) and a benzazepine ring system (rings A and B), which is linked by its C3 alcohol function to a chiral oxygenated side chain by a carboxylic function alpha to a tetrasubstituted carbon center. The botanical distribution of these alkaloids is limited to the Cephalotaxus genus (Cephalotaxaceae). The scope of biological activities of the Cephalotaxus alkaloids is mainly centered on the antileukemic activity of homoharringtonine (HHT) (2), which in particular demonstrated marked benefits in the treatment of orphan myeloid leukemia and was approved as soon as 2009 by European Medicine Agency and by US Food and Drug Administration in 2012. Its exact mechanism of action was partly elucidated and it was early recognized that HHT (2) inhibited protein synthesis at the level of the ribosome machinery. Interestingly, after a latency period of two decades, the topic of Cephalotaxus alkaloids reemerged as a prolific source of new natural structures. To date, more than 70 compounds have been identified and characterized. Synthetic studies also regained attention during the past two decades, and numerous methodologies were developed to access the first semisynthetic HHT (2) of high purity suitable for clinical studies, and then high grade enantiomerically pure CET (1), HHT (2), and analogs.
Topics: Animals; Antineoplastic Agents, Phytogenic; Harringtonines; Humans
PubMed: 28838429
DOI: 10.1016/bs.alkal.2017.07.001 -
Journal of the American College of... Oct 2017The clinical use of ivabradine has and continues to evolve along channels that are predicated on its mechanism of action. It selectively inhibits the funny current (I)... (Review)
Review
The clinical use of ivabradine has and continues to evolve along channels that are predicated on its mechanism of action. It selectively inhibits the funny current (I) in sinoatrial nodal tissue, resulting in a decrease in the rate of diastolic depolarization and, consequently, the heart rate, a mechanism that is distinct from those of other negative chronotropic agents. Thus, it has been evaluated and is used in select patients with systolic heart failure and chronic stable angina without clinically significant adverse effects. Although not approved for other indications, ivabradine has also shown promise in the management of inappropriate sinus tachycardia. Here, the authors review the mechanism of action of ivabradine and salient studies that have led to its current clinical indications and use.
Topics: Benzazepines; Cardiovascular Agents; Cardiovascular Diseases; Cyclic Nucleotide-Gated Cation Channels; Heart Rate; Humans; Ivabradine
PubMed: 28958335
DOI: 10.1016/j.jacc.2017.08.038 -
Cardiovascular Drugs and Therapy Aug 2016Stable angina pectoris affects 2-4 % of the population in Western countries and entails an annual risk of death and nonfatal myocardial infarction of 1-2 % and 3 %,... (Review)
Review
Stable angina pectoris affects 2-4 % of the population in Western countries and entails an annual risk of death and nonfatal myocardial infarction of 1-2 % and 3 %, respectively. Heart rate (HR) is linearly related to myocardial oxygen consumption and coronary blood flow, both at rest and during stress. HR reduction is a key target for the prevention of ischemia/angina and is an important mechanism of action of drugs which are recommended as first line therapy for the treatment of angina in clinical guidelines. However, many patients are often unable to tolerate the doses of beta blocker or non-dihydropyridine calcium antagonists required to achieve the desired symptom control. The selective pacemaker current inhibitor ivabradine was developed as a drug for the management of patients with angina pectoris, through its ability to reduce HR specifically. The available data suggest that ivabradine is a well-tolerated and effective anti-anginal agent and it is recommended as a second-line agent for relief of angina in guidelines. However, recent clinical trials of ivabradine have failed to show prognostic benefit and have raised potential concerns about safety. This article will review the available evidence base for the current role of ivabradine in the management of patients with symptomatic angina pectoris in the context of stable coronary artery disease.
Topics: Angina Pectoris; Benzazepines; Cardiovascular Agents; Drug Interactions; Drug Therapy, Combination; Heart Rate; Humans; Ivabradine
PubMed: 27475447
DOI: 10.1007/s10557-016-6678-x -
Therapeutic Advances in Respiratory... Oct 2008Tobacco dependence is a chronic relapsing disease that needs continuous treatment. In combination with behavioural support, pharmacotherapy is a proven key component for... (Review)
Review
Tobacco dependence is a chronic relapsing disease that needs continuous treatment. In combination with behavioural support, pharmacotherapy is a proven key component for supporting smoking cessation. Effective drugs are available and recommended: nicotine replacement therapy (NRT), bupropion and varenicline. Much research into new pharmacological approaches is ongoing, combining 'old' and 'new' drugs and personalizing a pharmacological treatment for a single smoker/patient; other new medications and vaccines are in development. Overall, pharmacotherapy seems to have efficacy and cost-effectiveness in real life, thus physicians should become familiar with these medicines. Further efforts should be aimed at optimizing treatment management and increasing smoking cessation rates in the general population.
Topics: Adrenergic Uptake Inhibitors; Antidepressive Agents, Tricyclic; Benzazepines; Bupropion; Humans; Nortriptyline; Piperidines; Pyrazoles; Quinoxalines; Randomized Controlled Trials as Topic; Rimonabant; Smoking Cessation; Treatment Outcome; Varenicline
PubMed: 19124379
DOI: 10.1177/1753465808096136 -
Circulation Journal : Official Journal... Jun 2022
Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Humans; Tolvaptan
PubMed: 35545552
DOI: 10.1253/circj.CJ-22-0194 -
CMAJ : Canadian Medical Association... Mar 2011
Comparative Study Randomized Controlled Trial
Topics: Adolescent; Age Factors; Benzazepines; Breast Neoplasms; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypertension; Lymph Nodes; Male; Quinoxalines; Risk Assessment; Sentinel Lymph Node Biopsy; Smoking Cessation; Survival Rate; Treatment Outcome; Varenicline
PubMed: 21422142
DOI: 10.1503/cmaj.110333 -
The New England Journal of Medicine Nov 2008A 57-year-old man with a 60-pack-year history visits his primary care provider because he wants to quit smoking. He has a history of stable coronary artery disease,... (Review)
Review
A 57-year-old man with a 60-pack-year history visits his primary care provider because he wants to quit smoking. He has a history of stable coronary artery disease, peripheral vascular disease, and hypertension. He also has severe obstructive lung disease (forced expiratory volume in 1 second, 39% of the predicted value) with a progressive increase in dyspnea. He has quit smoking and has had numerous relapses; the longest duration of abstinence from smoking was 7 months. Each relapse involved casual smoking to “test himself.” During previous attempts to quit, he has used a nicotine patch, a nicotine inhaler, and sustained-release bupropion. He feels motivated to quit smoking because he recently heard about a new medication to aid in quitting, and he wants to improve his health. The patient and his physician discuss the therapeutic options and agree that varenicline (Chantix) may be an option.
Topics: Benzazepines; Brain; Coronary Artery Disease; Humans; Male; Middle Aged; Motivation; Nicotine; Nicotinic Agonists; Practice Guidelines as Topic; Pulmonary Disease, Chronic Obstructive; Quinoxalines; Receptors, Nicotinic; Smoking Cessation; Tobacco Use Disorder; Varenicline
PubMed: 18987369
DOI: 10.1056/NEJMct0800146 -
International Journal of Molecular... Feb 2023Cardiac remodeling can cause ventricular dysfunction and progress to heart failure, a cardiovascular disease that claims many lives globally. Ivabradine, a funny channel... (Review)
Review
Cardiac remodeling can cause ventricular dysfunction and progress to heart failure, a cardiovascular disease that claims many lives globally. Ivabradine, a funny channel (I) inhibitor, is used in patients with chronic heart failure as an adjunct to other heart failure medications. This review aims to gather updated information regarding the therapeutic use and mechanism of action of ivabradine in heart failure. The drug reduces elevated resting heart rate, which is linked to increased morbidity and mortality in patients with heart failure. Its use is associated with improved cardiac function, structure, and quality of life in the patients. Ivabradine exerts several pleiotropic effects, including an antiremodeling property, which are independent of its principal heart-rate-reducing effects. Its suppressive effects on cardiac remodeling have been demonstrated in animal models of cardiac remodeling and heart failure. It reduces myocardial fibrosis, apoptosis, inflammation, and oxidative stress as well as increases autophagy in the animals. It also modulates myocardial calcium homeostasis, neurohumoral systems, and energy metabolism. However, its role in improving heart failure remains unclear. Therefore, elucidating its molecular mechanisms is imperative and would aid in the design of future studies.
Topics: Animals; Ivabradine; Ventricular Remodeling; Quality of Life; Benzazepines; Heart Rate; Heart Failure
PubMed: 36769115
DOI: 10.3390/ijms24032801 -
British Journal of Clinical Pharmacology Jan 2012
Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Humans; Hyponatremia; Inappropriate ADH Syndrome; Tolvaptan
PubMed: 21623874
DOI: 10.1111/j.1365-2125.2011.04029.x -
Turk Kardiyoloji Dernegi Arsivi : Turk... Apr 2015Hyponatremia is the most prevalent electrolyte imbalance, and may be present in up to 30% of hospitalized patients. It is an important predictor of in-hospital... (Review)
Review
Hyponatremia is the most prevalent electrolyte imbalance, and may be present in up to 30% of hospitalized patients. It is an important predictor of in-hospital mortality. Irrespective of the reason underlying hyponatremia, water metabolism plays an important role. Arginine-vasopressin, which has cardiovascular effects and plays a role in water metabolism, is released from the posterior hypothalamus in response to an increase in plasma osmolality or a drop in the blood pressure, which are detected by osmoreceptors and baroreceptors respectively. Arginine-vasopressin has receptors located on vascular smooth muscle cells, the heart (V1a), the collecting ducts of the renal medulla (V2), the anterior pituitary gland (V1b) and many other organs. Arginine-vasopressin antagonists, known as "vaptans", have recently attracted attention for the treatment of chronic hypotonic hyponatremia. In this review, we focus on the diagnosis and classification of hyponatremia, current trends in its treatment in the light of guidelines, and the rationale of using vaptans in treating hyponatremia. We also briefly review cornerstone studies in the literature regarding vaptans, and the correct indications, contraindications and cautions in the use of "tolvaptan" and "conivaptan", two approved vaptans for this indication.
Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Contraindications; Humans; Hyponatremia; Tolvaptan
PubMed: 25906004
DOI: 10.5543/tkda.2015.71508