Abstract:
:Most heterosexual women want to reduce the risk of acquiring a sexually transmitted infection; many also want to control their fertility. Several chemical agents have been proposed to dramatically slow the spread of HIV infections. Ideally, vaginal microbicides, with or without contraceptive properties, should be safe, effective, and affordable for women everywhere. Amphiphiles, which are surfactants that can act as detergents, have a long history as microbicides against many pathogens. Amphiphiles have several desirable traits; e.g., they are inexpensive, fast-acting, and capable of a broad spectrum of activity. An "ideal" amphiphilic microbicide will rapidly and selectively inactivate pathogens and sperm without irritating tissue. In this review, we discuss a homologous series of amphiphilic acylcarnitine analogues as microbicides. Two homologues, Z-14 and Z-15, possess excellent spermicidal, anti-HIV, anti-chlamydial, anti-gonorrhea, and anti-Haemophilus activities; both have outstanding anti-Candida activity. A 4% Z-15 gel that is comprised of 3% carboxymethylcellulose in water gives a dramatically low score in a rabbit-vaginal-irritation study. The mechanisms of action of these compounds are not fully understood as yet, but we present several possibilities. Moreover, the results of our limited structure-activity study with a homologous series have stimulated additional questions and ideas for designing the next generation of microbicidal amphiphiles. The above studies support the idea that Z-14 and Z-15 can potentially serve as safe (non-irritating), effective topical microbicides.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Gandour RDdoi
10.2174/138161205774580705subject
Has Abstractpub_date
2005-01-01 00:00:00pages
3757-67issue
29eissn
1381-6128issn
1873-4286journal_volume
11pub_type
杂志文章,评审abstract::The common mechanism of action of aspirin and the chemically unrelated non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of prostaglandin (PG) production due to interference with the enzymatic activity of cyclooxygenase (COX). These agents have long been used as effective treatments for arthritis. The r...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003398753
更新日期:2000-11-01 00:00:00
abstract::All common contributing factors to epilepsy such as trauma, malignancies and infections are accompanied by different levels of central nervous system inflammation that in turn have been associated with the occurrence of seizure. Emerging data from human brain tissue and experimental models of epilepsy support the prop...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319380009
更新日期:2013-01-01 00:00:00
abstract::An important goal of biomedical research is to translate basic research findings into practical clinical implementation. Despite the advances in the technology used in drug discovery, the development of drugs for central nervous system diseases remains challenging. The failure rate for new drugs targeting important ce...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200224112534
更新日期:2020-01-01 00:00:00
abstract::The review describes key aspects of the synthesis and biological activities of conjugates of oligonucleotides and their analogues with synthetic peptides, in particular aimed towards gene silencing applications. The common methods of synthesis of oligonucleotide-peptide conjugates (OPCs) and PNA-peptide conjugates (PP...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161205774580769
更新日期:2005-01-01 00:00:00
abstract::Urological cancer refers to cancer in organs of the urinary system and the male reproductive system. It mainly includes prostate cancer, bladder cancer, renal cancer, etc., seriously threatening patients' survival. Although there are many advances in the treatment of urological cancer, approved targeted therapies ofte...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200403131514
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Fragile X syndrome (FXS) is the most common form of monogenic hereditary cognitive impairment, including intellectual disability, autism, hyperactivity, and epilepsy. METHODS:This article reviews the literature pertaining to the role of synaptic dysfunction in FXS. RESULTS:In FXS, synaptic dysfunction alte...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191102165206
更新日期:2019-01-01 00:00:00
abstract::The term endozepines designates a family of astroglia-secreted proteins including the diazepambinding inhibitor (DBI) and its processing products, which have been originally isolated and characterized as endogenous ligands of benzodiazepine receptors. It is now clearly established that the octadecaneuropeptide ODN (DB...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666181112111746
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:The use of essential oils is receiving increasing attention worldwide, as these oils are good sources of several bioactive compounds. Nowadays essential oils are preferred over synthetic preservatives thanks to their antioxidant and antimicrobial properties. Several studies highlight the beneficial effect of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200121092018
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Origanum vulgare is used in Armenian cuisine as well as in folk medicine. The aim of this investigation was to determine the peculiarities of the chemical composition of Armenian flora's oregano essential oil (EO) and ethanol extract (EE) and to characterize mainly antioxidant and antibacterial properties in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666190702095612
更新日期:2019-01-01 00:00:00
abstract::Immune activation not only accompanies inflammation in various disorders including infections, autoimmune syndromes and cancer, but it also represents a characteristic feature of ageing. Immune deviations which are most widely expressed in the elderly include increased neopterin production and tryptophan breakdown. Th...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140317110217
更新日期:2014-01-01 00:00:00
abstract::The three opioid receptors, mu, delta and kappa all mediate analgesia, and knockout mice with opioid receptor deletion have proven unique tools to investigate in vivo opioid pharmacology. Since a few years, a number of new mouse lines have been engineered, with several distinct mutations of the mu receptor, to assess ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161281942140105163727
更新日期:2013-01-01 00:00:00
abstract::Neuromuscular blocking agents are the leading drugs responsible for immediate hypersensitivity reactions during anaesthesia. Most hypersensitivity reactions represent IgE-mediated allergic reactions. Their incidence is estimated to be between 1 in 3,000 to 1 in 110,000 general anaesthetics. However striking variations...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786369704
更新日期:2008-01-01 00:00:00
abstract::Release of acetylcholine from parasympathetic nerves in the airways activates postjunctional muscarinic receptors present on smooth muscle, submucosal glands and blood vessels. This triggers bronchoconstriction, muscle hypertrophy, mucus secretion, and vasodilatation, respectively. The release of acetylcholine from pa...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811209023061
更新日期:2012-01-01 00:00:00
abstract::There is growing evidence for the involvement of glutamatergic abnormalities in schizophrenia. Uncompetitive NMDA receptor (NMDAR) antagonists induce effects closely resembling both the positive and negative symptoms of schizophrenia; candidate risk genes for schizophrenia converge on the NMDAR expressing synapse; and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788957438
更新日期:2009-01-01 00:00:00
abstract::This article reviews evidence that hyperpolarization-activated, cation nonselective (HCN) channels, the molecular basis of the Ih current, potentially represent valid targets for novel analgesic agents. Ih is a prominent current in many peripheral sensory nerves, with highest current density typically found in large d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788489122
更新日期:2009-01-01 00:00:00
abstract::Genetic variation in the receptors and other intracellular targets that mediate the pharmacodynamic effects of drugs can affect therapeutic outcomes. However, at present greater knowledge is available concerning the extent of gene variation in drug metabolizing enzymes that determine drug pharmacokinetics and, in turn...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210790112674
更新日期:2010-01-01 00:00:00
abstract::Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes which catalyze CO(2) hydration to bicarbonate and protons. Five genetically distinct classes are known, which represent an excellent example of convergent evolution. Inhibition of α-CAs from vertebrates, including humans, with sulfonamides was exploited clinical...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210793429797
更新日期:2010-01-01 00:00:00
abstract::In recent years several new drugs (oxcarbazepine, lamotrigine, topiramate, gabapentin, zonisamide, tiagabine, fosphenytoin, vigabatrin and felbamate) have been added to the therapeutic armamentarium against epilepsy. Some of these represent structural modifications of pre-existing compounds, others were developed with...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003400245
更新日期:2000-05-01 00:00:00
abstract::In recent years, Aβ aggregation prevention, one of the most concerned strategies in drug development has been carefully assessed to treat Alzheimer's disease. Aβ peptides can transform structurally from random coil monomer into β-stranded protofibril via multiple oligomeric states. Among the various Aβ species, the id...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180813093420
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:A mobile health application is an exciting, fast-paced domain that is likely to improve prenatal care. METHODS:In this narrative review, we summarise the use of mobile health applications in this setting with a special emphasis on both the benefits of remote monitoring devices and the potential pitfalls of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190320140659
更新日期:2019-01-01 00:00:00
abstract::The clinically most relevant medications for lipid management are the statins, which constitute in the majority of the cases the basis of any lipid-modulating therapy. However, other agents are often needed to either reduce low-density cholesterol to target levels and/or to treat residual serum lipoprotein abnormaliti...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319170017
更新日期:2013-01-01 00:00:00
abstract::Over the last 15 years, the use of various biological therapies has largely improved the way we manage patients with Inflammatory Bowel Diseases (IBDs). Blockade of cytokine synthesis and/or activity is at the forefront of this new era with the success of inhibitors of tumor necrosis factor (TNF)-α. These therapies ar...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210794079164
更新日期:2010-01-01 00:00:00
abstract::The present review discusses the mechanism of late stent thrombosis and its distinction from restenosis and summarizes the advisory note issued by FDA on the proper usage of different treatments available for atherosclerosis. In light of the latest developments, a plethora of new stents have been and continue to be de...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208785294573
更新日期:2008-01-01 00:00:00
abstract::Opiates lack potent analgesic efficacy in neuropathic pain although it is now generally accepted that the poor effect of these drugs reflects a reduction in their potency. Reduction of morphine antinociceptive potency was postulated to be due to the fact that nerve injury altered the activity of opioid systems or opio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054865055
更新日期:2005-01-01 00:00:00
abstract::Cardiac arrhythmias remain a major source of morbidity and mortality in developed countries. Antiarrhythmic drug therapy was traditionally the mainstay of cardiac arrhythmia treatment; however, drug therapy of cardiac arrhythmias has been plagued by incomplete efficacy and by potentially serious adverse reactions, of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054021051
更新日期:2005-01-01 00:00:00
abstract::A large body of evidence on brain development and ageing has revealed that inflammatory processes profoundly affect brain functions during life span of mammalians, including humans. Activation of innate immune mechanisms leading to pro-inflammatory cytokine up-regulation is involved in devastating and disabling human ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210794519147
更新日期:2010-01-01 00:00:00
abstract::Prostacyclin (PGI(2)) is one of the major vascular protectors against thrombosis and vasoconstriction, caused by thromboxane A(2). Understanding the molecular mechanisms of PGI(2) biosynthesis and signaling is crucial to the development of therapeutic approaches to regulate PGI(2) functions. This review provides infor...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206776055994
更新日期:2006-01-01 00:00:00
abstract::The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases ca...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797247541
更新日期:2011-01-01 00:00:00
abstract::The rise of multi-drug resistant and extensively drug resistant M. tuberculosis around the world poses a great threat to human health, and necessitates development of new, effective and inexpensive anti-tubercular agents. The availability of knowledge on molecular biology of M. tuberculosis infection coupled with whol...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612819666131118165427
更新日期:2014-01-01 00:00:00
abstract::Angiogenesis, the development of new capillaries form pre-existing vessels, requires the coordinate activation of endothelial cells, which migrate and proliferate in response to growth factors to form functional vessels. Therapeutic angiogenesis is proposed to restore tissue integrity and function following damage and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033391405
更新日期:2003-01-01 00:00:00