Abstract:
:Schizophrenia is a chronic psychiatric disorder that affects about 1 in 100 people around the world and results in persistent emotional and cognitive impairments. Untreated schizophrenia leads to deterioration in quality of life and premature death. Although the clinical efficacy of dopamine D2 receptor antagonists against positive symptoms of schizophrenia supports the dopamine hypothesis of the disease, the resistance of negative and cognitive symptoms to these drugs implicates other systems in its pathophysiology. Many studies suggest that abnormalities in glutamate homeostasis may contribute to all three groups of schizophrenia symptoms. Scientific considerations also include disorders of gamma-aminobutyric acid-ergic and serotonergic neurotransmissions as well as the role of the immune system. The purpose of this review is to update the most recent reports on the discovery and development of non-dopaminergic agents that may reduce positive, negative, and cognitive symptoms of schizophrenia, and may be alternative to currently used antipsychotics. This review collects the chemical structures of representative compounds targeting metabotropic glutamate receptor, gamma-aminobutyric acid type A receptor, alpha 7 nicotinic acetylcholine receptor, glycine transporter type 1 and glycogen synthase kinase 3 as well as results of in vitro and in vivo studies indicating their efficacy in schizophrenia. Results of clinical trials assessing the safety and efficacy of the tested compounds have also been presented. Finally, attention has been paid to multifunctional ligands with serotonin receptor affinity or phosphodiesterase inhibitory activity as novel strategies in the search for dedicated medicines for patients with schizophrenia.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Jankowska A,Satała G,Partyka A,Wesołowska A,Bojarski AJ,Pawłowski M,Chłoń-Rzepa Gdoi
10.2174/0929867326666190710172002subject
Has Abstractpub_date
2019-01-01 00:00:00pages
4885-4913issue
25eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-99546journal_volume
26pub_type
杂志文章,评审abstract::Developing suitable medicines for genetic diseases requires a detailed understanding of not only the pathways that cause the disease, but also the identification of the genetic components involved in disease manifestation. This article focuses on the complexities associated with ocular ciliopathies - a class of debili...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180917102557
更新日期:2019-01-01 00:00:00
abstract::A dramatical decline in human male reproductive function has been reported for the past 20 years. Many recent epidemiological, clinical and experimental findings suggest that the reproductive dysfunction could result from prenatal and neonatal chemical compound exposure. Even if numerous studies argue for a relationsh...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711797636117
更新日期:2011-01-01 00:00:00
abstract::Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hybrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can result in compounds pres...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707781058805
更新日期:2007-01-01 00:00:00
abstract::Fourier-transform infrared (FT-IR) based mapping and imaging is a fast emerging technology which is being increasingly applied to investigate tissues in the high-throughput mode. The high resolution close to the cellular level, the possibility to determine the bio-distribution of molecules of interest (proteins, pepti...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709787002664
更新日期:2009-01-01 00:00:00
abstract::The alphavbeta3 receptor, which are members of the group of the cellular adhesion molecules (CAM), are heterodimeric transmembrane glycoprotein receptors involved in processes such as cell-cell and cell-matrix adhesion, cell migration and signaling. Integrin alphavbeta3 receptor is expressed on almost all cells origin...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867053363522
更新日期:2005-01-01 00:00:00
abstract::Bioactivation of xenobiotics can, in certain circumstances, result in the formation of reactive electrophilic species. These reactive metabolites may covalently modify proteins and macromolecules and it has been suggested that protein modification is a key initial step in provoking idiosyncratic adverse drug reactions...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711796391714
更新日期:2011-01-01 00:00:00
abstract::It is now widely accepted that airway inflammation is the key factor underlying the pathogenesis of asthma. Inhaled corticosteroids remain the most important anti-inflammatory treatment for asthma. However, they are rather non-specific in their actions and their use raises concerns over side effects and compliance iss...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706778521779
更新日期:2006-01-01 00:00:00
abstract::The evidence seems to be growing in favor of the stem cell theory of cancer with the emergence of studies demonstrating the parallel mechanisms of self renewing pathways in stem cells and particular subsets of cancer cells. The finding of leukemia stem cells and subsequently breast cancer stem cells (BCSC) further sup...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712804485863
更新日期:2012-01-01 00:00:00
abstract::Tetracyclines (TCs) and their non-antimicrobial analogs (CMTs) have therapeutic potential to inhibit tissue destructive disease processes, such as cancer invasion and metastasis, by inhibiting certain matrix metalloproteinases. Enhanced matrix metalloproteinase-2 (MMP-2; gelatinase A) activity has been correlated to c...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867013373660
更新日期:2001-02-01 00:00:00
abstract::Ca(2+) is a highly versatile intracellular second messenger in the central nervous system, and regulates many complicated cellular processes, including excitation, plasticity and apoptosis. Influx of Ca(2+) from the extracellular fluid is required for sustained elevation of the cytosolic Ca(2+) concentration and full ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712803341430
更新日期:2012-01-01 00:00:00
abstract::Resistance to quinolones and fluoroquinolones has been increasingly reported among human and veterinary isolates during the last three decades related to their wide clinical use. Until recently, the mechanisms of resistance to quinolones in Enterobacteriaceae were believed to be only chromosome-encoded, i.e. related t...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709787581879
更新日期:2009-01-01 00:00:00
abstract::Human immunodeficiency virus (HIV) infection commonly results in a myriad of comorbid conditions secondary to immune deficiency. Infection also affects broad organ system function. Although current antiretroviral therapy (ART) reduces disease morbidity and mortality through effective control of peripheral viral load, ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867321666140826114135
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Research on Chromogranin A (CGA) and its derived fragments convincingly demonstrated the multifunctional activity of the 21 amino acid peptide named Catestatin (CST: human CGA352-372, bovine CGA344-364, rat CGA367-387). This review aims to provide a synopsis of the current information concerning the biologic...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170616104759
更新日期:2017-01-01 00:00:00
abstract::Despite advances in cancer treatment, a large number of patients eventually develop metastatic disease that is generally incurable. Systemic chemotherapy remains the standard treatment for these patients. Several chemotherapeutic combinations have proven effective in the management of cancer. Paradoxically, although t...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712800099820
更新日期:2012-01-01 00:00:00
abstract::The stilbene scaffold is a basic element for a number of biologically active natural and synthetic compounds, and it is considered as a privileged structure. Stilbenes exemplified by resveratrol, combretastatin A-4 and pterostilbene are of significant interest for drug research and development because of their potenti...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666160517121629
更新日期:2016-01-01 00:00:00
abstract::Nitric oxide (NO) has been established as an important messenger molecule in various steps of brain physiology, from development to synaptic plasticity, learning and memory. However, NO has also been viewed as a major agent of neuropathology when, escaping controlled production it may directly or indirectly promote ox...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033456792
更新日期:2003-10-01 00:00:00
abstract::The use of antisense oligonucleotides as therapeutic agents has generated considerable enthusiasm in the research and medical community. Antisense oligonucleotides as therapeutic agents were proposed as far back as in the 1970s when the antisense strategy was initially developed. Nonetheless, it has taken almost a qua...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867054864859
更新日期:2005-01-01 00:00:00
abstract::Many non-cardiovascular drugs of common clinical use cause, as an unwanted accessory property, the prolongation of the cardiac repolarisation process, due to the block of the HERG (Human Ether-a-go-go Related Gene) potassium channel, responsible for the repolarising I(Kr) current. This delayed cardiac repolarisation p...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867043364351
更新日期:2004-10-01 00:00:00
abstract::The hyaluronidases (HAases) are a group of less extensively studied glycosidases distributed throughout the animal kingdom and are popularly known as 'spreading factors'. In recent years, HAases received much attention due to their ability to abruptly alter the hyaluronic acid (HA) homeostasis. HAases preferentially d...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709788453078
更新日期:2009-01-01 00:00:00
abstract::To this point, efforts to develop therapeutic peptides for intracellular applications were guided by the perception that unmodified linear peptides are highly unstable and therefore structural modifications are required to reduce proteolytic breakdown. Largely, this concept is a consequence of the fact that most resea...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170508143523
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Smac mimetics (also known as IAP antagonist) are a new class of targeted drugs having a goal to suppress the IAPs, reestablishing the apoptotic pathways and inducing cancer cell death. Therefore, development of Smac mimetics was considered an attractive strategy for the development of new anticancer drugs. L...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180313112229
更新日期:2018-01-01 00:00:00
abstract::The focus of this review is the cellular internalisation mechanism of nanostructured systems (NSs) and their endosomal escape for targeted drug delivery. Endocytosis is a cellular process of internalisation of different molecules and foreign microorganisms. It is currently being studied for drug delivery through nanos...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170214111205
更新日期:2017-01-01 00:00:00
abstract::Universal stress proteins are ubiquitously expressed in bacteria, archaea and plants and other eukaryotes. A general property of USPs is their role in adaptation of bacteria to oxidative stress, high temperature, low pH and/or hypoxia. There is increasing evidence that these proteins facilitate the adaption of bacteri...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170124145543
更新日期:2017-11-24 00:00:00
abstract::In order to ascertain the role of dietary flavonoids as antioxidants in vivo it is necessary to understand the chemical nature of the absorbed forms in the circulation in vivo and how the multiplicity of research findings in vitro reflect the bioactivity of flavonoids in vivo. Only when we gain adequate information on...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867013373011
更新日期:2001-06-01 00:00:00
abstract::Small conductance Ca(2+)-activated K(+) (SK(Ca)) channels comprise an important subclass of K(+) channels. Selective blockade of SK(Ca) channels may find application in the therapy of myotonic muscular dystrophy, gastrointestinal dysmotilities, memory disorders, narcolepsy, and alcohol abuse. In the cyclophanes descri...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708784534983
更新日期:2008-01-01 00:00:00
abstract::Essential oils constituents are a diverse family of low molecular weight organic compounds with comprehensive biological activity. According to their chemical structure, these active compounds can be divided into four major groups: terpenes, terpenoids, phenylpropenes, and "others". In addition, they may contain diver...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180330092607
更新日期:2020-01-01 00:00:00
abstract::The mitotic cell cycle is a tightly regulated process that ensures the correct division of one cell into two daughter cells. Progress along the different phases of the cell cycle is positively regulated by the sequential activation of a family of serine-threonine kinases called CDKs (Cyclin Dependent Kinases). Their a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867054367149
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Polyphenols are probably the most known and investigated molecules of nutritional interest as micronutrients present in abundance in our diet. Some of the most important food sources of polyphenols in the Mediterranean diet are olives and olive oil. A growing body of evidence from animal models to clinical s...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666160627104022
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Visible light is absorbed by photoacceptors in pigmented and non-pigmented mammalian cells, activating signaling cascades and downstream mechanisms that lead to the modulation of cellular processes. Most studies have investigated the molecular mechanisms and therapeutic applications of UV and the red to near...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170727112206
更新日期:2018-01-01 00:00:00
abstract::Poly(aminoester) dendrimers are expected to hold great promise as biodegradable nanocarriers for drug delivery due to their advantageous properties allowing their biodegradability, potentially lower toxicity and possibility of diverse chemical conjugations. The synthetic strategies for constructing such dendrimers inc...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867311209025011
更新日期:2012-01-01 00:00:00