Guide to Receptors and Channels (GRAC), 3rd edition.
TL;DR: The Fifth Edition of the 'Guide to Receptors and Channels' is a compilation of the major pharmacological targets divided into seven sections: G protein-coupled receptors, ligand-gated ion channels, ion channel, catalytic receptors, nuclear receptors, transporters and enzymes.
Abstract: The Fifth Edition of the 'Guide to Receptors and Channels' is a compilation of the major pharmacological targets divided into seven sections: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside suggestions for further reading. Available alongside this publication is a portal at http://www.GuideToPharmacology.org which is produced in close association with NC-IUPHAR and allows free online access to the information presented in the Fifth Edition.
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TL;DR: ChEMBL is an Open Data database containing binding, functional and ADMET information for a large number of drug-like bioactive compounds to maximize their quality and utility across a wide range of chemical biology and drug-discovery research problems.
Abstract: ChEMBL is an Open Data database containing binding, functional and ADMET information for a large number of drug-like bioactive compounds. These data are manually abstracted from the primary published literature on a regular basis, then further curated and standardized to maximize their quality and utility across a wide range of chemical biology and drug-discovery research problems. Currently, the database contains 5.4 million bioactivity measurements for more than 1 million compounds and 5200 protein targets. Access is available through a web-based interface, data downloads and web services at: https://www.ebi.ac.uk/chembldb.
2,956 citations
TL;DR: This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non- CB1, non-CB2 established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors.
Abstract: There are at least two types of cannabinoid receptors (CB1 and CB2). Ligands activating these G protein-coupled receptors (GPCRs) include the phytocannabinoid Δ9-tetrahydrocannabinol, numerous synthetic compounds, and endogenous compounds known as endocannabinoids. Cannabinoid receptor antagonists have also been developed. Some of these ligands activate or block one type of cannabinoid receptor more potently than the other type. This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non-CB1, non-CB2 established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors. From these data, it is clear that some ligands that interact similarly with CB1 and/or CB2 receptors are likely to display significantly different pharmacological profiles. The review also lists some criteria that any novel “CB3” cannabinoid receptor or channel should fulfil and concludes that these criteria are not currently met by any non-CB1, non-CB2 pharmacological receptor or channel. However, it does identify certain pharmacological targets that should be investigated further as potential CB3 receptors or channels. These include TRP vanilloid 1, which possibly functions as an ionotropic cannabinoid receptor under physiological and/or pathological conditions, and some deorphanized GPCRs. Also discussed are 1) the ability of CB1 receptors to form heteromeric complexes with certain other GPCRs, 2) phylogenetic relationships that exist between CB1/CB2 receptors and other GPCRs, 3) evidence for the existence of several as-yet-uncharacterized non-CB1, non-CB2 cannabinoid receptors; and 4) current cannabinoid receptor nomenclature.
1,439 citations
Cites background from "Guide to Receptors and Channels (GR..."
...mendations of the International Union of Basic and Clinical Pharmacology nomenclature and also conforms to Alexander et al. (2009)....
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TL;DR: Particular focus will be placed on phytocannabinoid‐terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin‐resistant Staphylococcus aureus).
Abstract: Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL−1. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant.
LINKED ARTICLES
This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7
1,113 citations
Cites background from "Guide to Receptors and Channels (GR..."
...Nomenclature follows conventions in Alexander et al. (2009). Phytocannabinoids and terpenoids are synthesized in cannabis, in secretory cells inside glandular trichomes (Figure 1) that are most highly concentrated in unfertilized female flowers prior to senescence (Potter, 2004; Potter, 2009)....
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TL;DR: The International Union of Basic and Clinical Pharmacology/British Pharmacological Society (IUPHAR/BPS) Guide to PHARMACOLOGY is a new open access resource providing pharmacological, chemical, genetic, functional and pathophysiological data on the targets of approved and experimental drugs.
Abstract: The International Union of Basic and Clinical Pharmacology/British Pharmacological Society (IUPHAR/BPS) Guide to PHARMACOLOGY (http://www.guidetopharmacology.org) is a new open access resource providing pharmacological, chemical, genetic, functional and pathophysiological data on the targets of approved and experimental drugs. Created under the auspices of the IUPHAR and the BPS, the portal provides concise, peer-reviewed overviews of the key properties of a wide range of established and potential drug targets, with in-depth information for a subset of important targets. The resource is the result of curation and integration of data from the IUPHAR Database (IUPHAR-DB) and the published BPS 'Guide to Receptors and Channels' (GRAC) compendium. The data are derived from a global network of expert contributors, and the information is extensively linked to relevant databases, including ChEMBL, DrugBank, Ensembl, PubChem, UniProt and PubMed. Each of the ∼6000 small molecule and peptide ligands is annotated with manually curated 2D chemical structures or amino acid sequences, nomenclature and database links. Future expansion of the resource will complete the coverage of all the targets of currently approved drugs and future candidate targets, alongside educational resources to guide scientists and students in pharmacological principles and techniques.
851 citations
TL;DR: Designer β‐keto amphetamines (e.g. cathinones, ‘bath salts’ and ‘research chemicals’) have become popular recreational drugs, but their pharmacology is poorly characterized.
Abstract: Background and purpose: Designer beta-keto amphetamines (e.g., cathinones, "bath salts," and "research chemicals") have become popular recreational drugs, but their pharmacology is poorly characterized. Experimental approach: We determined the potencies of cathinones to inhibit dopamine (DA), noradrenaline (NA), and serotonin (5-hydroxytryptamine [5-HT]) transport into transporter-transfected human embryonic kidney 293 cells, DA and 5-HT efflux from monoamine-preloaded cells, and monoamine receptor binding affinity. Key results: Mephedrone, methylone, ethylone, butylone, and naphyrone act as nonselective monoamine uptake inhibitors, similar to cocaine. Mephedrone, methylone, ethylone, and butylone also release 5-HT, similar to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and other entactogens. Cathinone, methcathinone, and flephedrone act as preferential DA and NA uptake inhibitors and DA releasers, similar to amphetamine and methamphetamine. Pyrovalerone and 3,4-methylenedioxypyrovalerone (MDPV) are highly potent and selective DA and NA transporter inhibitors but unlike amphetamines do not release monoamines. The non-beta-keto amphetamines are trace amine-associated receptor 1 ligands, whereas cathinones are not. All cathinones showed high blood-brain barrier permeability in an in vitro model. Mephedrone and MDPV exhibited particularly high permeability. Conclusions and implications: Cathinones have considerable pharmacological differences that form the basis for their suggested classification into three groups. The predominant action of all cathinones on the DA transporter is likely associated with a considerable risk of addiction. (c) 2012 The Authors. British Journal of Pharmacology (c) 2012 The British Pharmacological Society.
595 citations
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"Guide to Receptors and Channels (GR..." refers background in this paper
...Where this guidance is lacking, advice from several prominent, independent experts has been obtained to produce an authoritative consensus, which attempts to fit in within the general guidelines from NC-IUPHAR (Vanhoutte et al., 1996)....
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...With each record, an indication is given of the status of the nomenclature, as proposed by Nomenclature Committees of the International Pharmacological Congress (NC-IUPHAR), published in Pharmacological Reviews....
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