Abstract:
:CB1 and CB2 cannabinoid receptors are the primary targets of endogenous cannabinoids (endocannabinoids). These G protein-coupled receptors play an important role in many processes, including metabolic regulation, craving, pain, anxiety, bone growth, and immune function. Cannabinoid receptors can be engaged directly by agonists or antagonists, or indirectly by manipulating endocannabinoid metabolism. In the past several years, it has become apparent from preclinical studies that therapies either directly or indirectly influencing cannabinoid receptors might be clinically useful. This review considers the components of the endocannabinoid system and discusses some of the most promising endocannabinoid-based therapies.
journal_name
Annu Rev Pharmacol Toxicoljournal_title
Annual review of pharmacology and toxicologyauthors
Mackie Kdoi
10.1146/annurev.pharmtox.46.120604.141254keywords:
subject
Has Abstractpub_date
2006-01-01 00:00:00pages
101-22eissn
0362-1642issn
1545-4304journal_volume
46pub_type
杂志文章,评审abstract::Originally, organophosphorus (OP) toxicology consisted of acetylcholinesterase inhibition by insecticides and chemical threat agents acting as phosphorylating agents for serine in the catalytic triad, but this is no longer the case. Other serine hydrolases can be secondary OP targets, depending on the OP structure, an...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010716-104926
更新日期:2017-01-06 00:00:00
abstract::Caveolae, a subset of membrane (lipid) rafts, are flask-like invaginations of the plasma membrane that contain caveolin proteins, which serve as organizing centers for cellular signal transduction. Caveolins (-1, -2, and -3) have cytoplasmic N and C termini, palmitolylation sites, and a scaffolding domain that facilit...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.48.121506.124841
更新日期:2008-01-01 00:00:00
abstract::Microbicides, substances applied topically to prevent sexual HIV infection, are needed to empower receptive sexual partners with effective prevention methods. Several large microbicide trials, however, failed to demonstrate efficacy, thus motivating a reevaluation of the current microbicide development paradigm, which...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.48.113006.094906
更新日期:2009-01-01 00:00:00
abstract::Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme ...
journal_title:Annual review of pharmacology and toxicology
pub_type:
doi:10.1146/annurev-pharmtox-091616-023708
更新日期:2017-01-06 00:00:00
abstract::Determining the potential toxicity of compounds early in the drug discovery process can be extremely beneficial in terms of both time and money conservation. Because of the speed of modern chemical synthesis and screening, to accurately evaluate the large number of compounds being produced, toxicology assays must have...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.40.1.335
更新日期:2000-01-01 00:00:00
abstract::Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and hav...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010716-104846
更新日期:2017-01-06 00:00:00
abstract::The recent advances made in elucidating the processes of nociception have altered the way that chronic pain therapy and analgesic drug development are approached. Recent studies have highlighted new targets for drug discovery, including inhibition of inflammatory mediators (kinins, growth factors), newly expressed pro...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.36.040196.001345
更新日期:1996-01-01 00:00:00
abstract::Transgenic rodent models for measuring mutations provide a tool for assessing tissue-specific mutations following in vivo treatment. These systems are based on the insertion into the rodent genome Escherichia coli lacI (lac repressor) or lacZ (beta-galactosidase) genes that serve as targets for mutations. Following in...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.35.040195.001045
更新日期:1995-01-01 00:00:00
abstract::Systems approaches have long been used in pharmacology to understand drug action at the organ and organismal levels. The application of computational and experimental systems biology approaches to pharmacology allows us to expand the definition of systems pharmacology to include network analyses at multiple scales of ...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010611-134520
更新日期:2012-01-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) represent a major class of proteins in the genome of many species, including humans. In addition to the mapping of a number of human disorders to regions of the genome containing GPCRs, a growing body of literature has documented frequently occurring variations (i.e. polymorphisms) ...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.41.1.593
更新日期:2001-01-01 00:00:00
abstract::Neuroglial cells of the central nervous system include the astrocytes, oligodendrocytes, and microglia. Their counterparts in the peripheral nervous system are the Schwann cells. The term neuroglia comes from an erroneous concept originally coined by Virchow (1850), in which he envisioned the neurons to be embedded in...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.39.1.151
更新日期:1999-01-01 00:00:00
abstract::Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are two Ca(2+) messengers derived from NAD and NADP, respectively. Although NAADP is a linear molecule, structurally distinct from the cyclic cADPR, it is synthesized by similar enzymes, ADP-ribosyl cyclase and its homolog, CD38. The c...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.41.1.317
更新日期:2001-01-01 00:00:00
abstract::Selective, nonpeptide antagonists for tachykinin receptors first became available ten years ago. Of the three known tachykinin receptors, drug development has focused most intensively on the substance P-preferring receptor, neurokinin(1) (NK(1)). Although originally studied as potential analgesic compounds, recent evi...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.41.1.877
更新日期:2001-01-01 00:00:00
abstract::A number of exciting findings have been made in astrocytes during the past 15 years that have led many researchers to redefine how the brain works. Astrocytes are now widely regarded as cells that propagate Ca(2+) over long distances in response to stimulation, and, similar to neurons, release transmitters (called gli...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.011008.145602
更新日期:2009-01-01 00:00:00
abstract::Oligonucleotides (ONs) can interfere with biomolecules representing the entire extended central dogma. Antisense gapmer, steric block, splice-switching ONs, and short interfering RNA drugs have been successfully developed. Moreover, antagomirs (antimicroRNAs), microRNA mimics, aptamers, DNA decoys, DNAzymes, synthetic...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010818-021050
更新日期:2019-01-06 00:00:00
abstract::The beta 3 subtype of adrenaline and noradrenaline receptors has now been extensively characterized at the structural and functional levels. Ligand binding and adenylyl cyclase activation studies helped define a beta-adrenergic profile that is quite distinct from that of the beta 1- and beta 2-adrenergic receptors, bu...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.37.1.421
更新日期:1997-01-01 00:00:00
abstract::Nuclear receptors (NR) are ligand-modulated transcription factors that play diverse roles in cell differentiation, development, proliferation, and metabolism and are associated with numerous liver pathologies such as cancer, steatosis, inflammation, fibrosis, cholestasis, and xenobiotic/drug-induced liver injury. The ...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010715-103209
更新日期:2016-01-01 00:00:00
abstract::The heptahelical G protein-coupled receptors (GPCRs) belong to the largest family of cell surface signaling receptors encoded in the human genome. GPCRs signal to diverse extracellular stimuli and control a vast number of physiological responses, making this receptor class the target of nearly half the drugs currently...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.48.113006.094646
更新日期:2008-01-01 00:00:00
abstract::The renin-angiotensin-aldosterone system is one of the most important systems in cardiovascular control and in the pathogenesis of cardiovascular diseases. Therefore, it is already a very successful drug target for the therapy of these diseases. However, angiotensins are generated not only in the plasma but also local...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.010909.105610
更新日期:2010-01-01 00:00:00
abstract::The RNA polymerase I (Pol I) transcription machinery in the nucleolus is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production that in turn guides cell growth and proliferation. Cancer cells commonly harbor mutations that ina...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.010909.105844
更新日期:2010-01-01 00:00:00
abstract::The protein variously named ABCG2/BCRP/MXR/ABCP is a recently described ATP-binding cassette (ABC) transporter originally identified by its ability to confer drug resistance that is independent of Mrp1 (multidrug-resistance protein 1) and Pgp (P-glycoprotein). Unlike Mrp1 and Pgp, ABCG2 is a half-transporter that must...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.46.120604.141238
更新日期:2006-01-01 00:00:00
abstract::Parkinson's disease (PD) is a chronic, progressive, disabling neurodegenerative disorder that begins in mid to late life and is characterized by motor impairment, autonomic dysfunction, and, in many, psychological and cognitive changes. Recent advances have helped delineate pathogenetic mechanisms, yet the cause of PD...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-011613-135937
更新日期:2014-01-01 00:00:00
abstract::Oral vaccination enables pain-free and self-administrable vaccine delivery for rapid mass vaccination during pandemic outbreaks. Furthermore, it elicits systemic and mucosal immune responses. This protects against infection at mucosal surfaces, which may further enhance protection and minimize the spread of disease. T...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章
doi:10.1146/annurev-pharmtox-030320-092348
更新日期:2021-01-06 00:00:00
abstract::Most facets of mammalian physiology and behavior vary according to time of day, thanks to endogenous circadian clocks. Therefore, it is not surprising that many aspects of pharmacology and toxicology also oscillate according to the same 24-h clocks. Daily oscillations in abundance of proteins necessary for either drug...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-011613-135923
更新日期:2014-01-01 00:00:00
abstract::Electron cryo-microscopy (cryo-EM) has revolutionized structure determination of membrane proteins and holds great potential for structure-based drug discovery. Here we discuss the potential of cryo-EM in the rational design of therapeutics for membrane proteins compared to X-ray crystallography. We also detail recent...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010919-023545
更新日期:2020-01-06 00:00:00
abstract::Bisphosphonates (BPs) are pyrophosphate analogs in which the oxygen bridge has been replaced by carbon and diverse carbon side chains have generated a large family of compounds. Several are potent inhibitors of bone destruction (resorption) and are in clinical use for the treatment and prevention of osteoporosis, Page...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.38.1.375
更新日期:1998-01-01 00:00:00
abstract::Behavioral consequences of low-level lead (Pb) exposure include impairments in learning processes and in Fixed-Interval schedule-controlled operant behavior. Although the neurobiological bases of these effects remain undetermined, current evidence suggests that inhibitory effects of Pb on the NMDA receptor complex may...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.35.040195.002135
更新日期:1995-01-01 00:00:00
abstract::Mutant ras oncogenes and alterations in the mitogenic signaling pathways that they regulate are associated with a wide variety of solid tumors and leukemias for which existing chemotherapeutics have limited utility. Of the possible approaches to inhibit Ras function, much attention has focused on a posttranslational m...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.37.1.143
更新日期:1997-01-01 00:00:00
abstract::Research on autophagy and its effects on cell metabolism and physiology has increased dramatically during recent years. Multiple forms of autophagy have been characterized, and many of the genes involved in the regulation of this process have been identified. The importance of autophagy for embryonic development and m...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-011112-140210
更新日期:2013-01-01 00:00:00
abstract::γ-Secretases are a group of widely expressed, intramembrane-cleaving proteases involved in many physiological processes. Their clinical relevance comes from their involvement in Alzheimer's disease, cancer, and other disorders. A clinical trial with the wide-spectrum γ-secretase inhibitor semagacestat has, however, de...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010814-124309
更新日期:2015-01-01 00:00:00