Abstract:
:The antiepileptic activity of α-substituted acetamides, lactams, and cyclic imides has been known for over six decades. We recently proposed an α-substituted amide group as the minimum pharmacophore responsible for inhibition of neuronal nicotinic acetylcholine receptors by these compounds, with the implication that inhibition of these receptors in the brain might be the unifying mechanism of action for these classes of antiepileptic drugs. In order to realize the pharmacological potential of these orally administered drugs, the relevant aspects of solid-state chemistry and pharmaceutics (including solubility and stability) need to be addressed. A better - more cohesive and generalized - understanding of the solid-state properties of these drugs would pave the road for a rational approach to their development, formulation, and manufacturing. In this paper, Pharmaceutically relevant aspects of the crystal structure and solid-state chemistry of antiepileptic drugs containing the α-substituted amide bond pharmacophore - α-substituted acetamides, lactams, and cyclic imides and the structurally related barbiturates, hydantoins, and acetylureas are reviewed. The applicable experimental and computational approaches are also briefly mentioned.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Krivoshein AVdoi
10.2174/1381612822666160722095748subject
Has Abstractpub_date
2016-01-01 00:00:00pages
5029-5040issue
32eissn
1381-6128issn
1873-4286pii
CPD-EPUB-77234journal_volume
22pub_type
杂志文章,评审abstract::Currently management of food allergy is mainly based on absolute avoidance of the offending food(s) and the use of rescue medication. However, the risk of severe or life-threatening reactions due to inadvertent exposure, nutritional imbalance and social isolation raises the demand of disease-modifying treatments. The ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990045
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abstract::The survival of patients with pulmonary arterial hypertension is closely related with right ventricular function. During the progression of right ventricular remodeling, energetic metabolism shifts from oxidative mitochondrial metabolism to glycolysis. In normal physiological conditions, cardiomyocytes use major sourc...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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abstract::Fibrate derivatives have a 40-year history in the management of dyslipidemia. Although this class of drugs is generally well tolerated, several safety issues have arisen from their use. In the present article we review the literature describing side effects associated with the use of fibrates except for those that are...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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abstract::Nitric oxide is a ubiquitous molecule involved in a variety of biological processes. The specific action of NO depends on its enzymatic sources namely neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) and all three isoforms have been localized in the gastrointestinal tract. Constit...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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abstract::The concept of probiotics has evolved immensely since it was first proposed a century ago. There are numerous potential health benefits attributed to certain probiotic bacteria, from preventing gastrointestinal (GI) infections to stimulating the immune system. Recent evidence is now quite compelling for a role of prob...
journal_title:Current pharmaceutical design
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abstract::The HIV/AIDS pandemic continues its spread at a rate of over 15,000 new infections every day. Sexual transmission of HIV-1 is the dominant mode of this pandemic spread. For the first time since the disease emerged in the early 1980s, about half the 42 million people now living with HIV/AIDS worldwide are women. Worldw...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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abstract::By updating John Littleton's work published 15 years ago this review summarizes recent work on pharmacodynamic aspects of acamprosate and the perspective for future developments. In addition to insights into the role of glutamatergic receptor systems, craving and relapse inspired by acamprosate, clinical research poin...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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abstract::Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can self-renew indefinitely, while maintaining the capacity to differentiate into useful somatic cell types, including cardiomyocytes. As such, these stem cell types represent an essentially inexhaustible source of committed human cardiomyo...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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更新日期:2015-01-01 00:00:00
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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abstract:BACKGROUND:Drugs acting on the cardiovascular and central nervous system often display relatively fast clinical responses, which may differ in neonates compared to children and adults. Introduction of bedside monitoring tools might be of additional value in the pharmacodynamic (PD) assessment of such drugs in neonates....
journal_title:Current pharmaceutical design
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doi:10.2174/1381612823666170918124419
更新日期:2017-01-01 00:00:00
abstract::Recent advances in DNA sequencing has made it possible to accurately decipher the entire genetic complement of a probiotic bacterium. Increases in sequencing capabilities have been enhanced through improved computer software that can annotate, or identify, the majority of genes encoded by the sequence. The availabilit...
journal_title:Current pharmaceutical design
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abstract::Integrins alpha(1)beta(1) and alpha(2)beta(1) are highly expressed on the microvascular endothelial cells, and blocking of their adhesive properties significantly reduced the VEGF-driven neovascularization ratio and tumor growth in animal models. Hence, inhibitors of the alpha(1)beta(1) and alpha(2) beta(1) integrins,...
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abstract:BACKGROUND:Type 1 diabetes is a chronic autoimmune disease featured by insulin deprivation caused by pancreatic β-cell loss, followed by hyperglycaemia. OBJECTIVE:Currently, there is no cure for this disease in clinical treatment, and patients have to accept a lifelong injection of insulin. The exploration of potentia...
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journal_title:Current pharmaceutical design
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更新日期:2014-01-01 00:00:00
abstract::A growing body of evidence shows that gamma-hydroxybutyric acid (GHB) is an addictive substance. Its precursors gammabutyrolactone (GBL) and 1,4-butanediol (1,4-BD) show the same properties and may pose even more risks due to different pharmacokinetics. There are indications that problematic GHB use is increasing in t...
journal_title:Current pharmaceutical design
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更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Polyphenols are bioactive compounds that can be found mostly in foods like fruits, cereals, vegetables, dry legumes, chocolate and beverages such as coffee, tea and wine. They are extensively used in the prevention and treatment of cardiovascular disease (CVD) providing protection against many chronic illnes...
journal_title:Current pharmaceutical design
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更新日期:2018-01-01 00:00:00
abstract::Diabetic macular edema (DME) represents the most common cause of vision loss in patients affected by diabetes mellitus. Although the pathophysiology of DME is not wholly understood, vascular endothelial growth factor (VEGF) has been identified as a key contributor to the development of DME. In addition, latest informa...
journal_title:Current pharmaceutical design
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更新日期:2015-01-01 00:00:00
abstract::Viral infections are important causes of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Some viruses, such as the respiratory and gastrointestinal viruses, are acquired from the healthcare or community in the midst of or after HSCT. Other viruses, such as the herpes-virus family, esta...
journal_title:Current pharmaceutical design
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abstract::Dioxygen (O2) is an exogenously supplied gas with a number of properties that make it valuable as a biological source of energy and as a result much of life has become dependent on this molecule. Nitric oxide (NO), carbon dioxide (CO) and hydrogen sulfide (H2S) are small molecules that are sometimes in a gaseous state...
journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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更新日期:2005-01-01 00:00:00
abstract::Reactive oxygen species (ROS) are well recognized for playing a dual role as both deleterious and beneficial species. ROS are products of normal cellular metabolism and under physiological conditions, participate in maintenance of cellular 'redox homeostasis. Overproduction of ROS, results in oxidative stress. Oxidati...
journal_title:Current pharmaceutical design
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更新日期:2012-01-01 00:00:00