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Article ; Online: Motor-like Tics are Mediated by CB

Gorberg, Victoria / Borisov, Veronika / Greig, Iain R / Pertwee, Roger G / McCaffery, Peter / Anavi-Goffer, Sharon

2022 Volume 59, Issue 8, Page(s) 5070–5083

Abstract: ... ...

Abstract	Δ
MeSH term(s)	Animals ; Dronabinol/pharmacology ; Endocannabinoids ; Female ; Humans ; Male ; Mice ; Monoacylglycerol Lipases ; Receptor, Cannabinoid, CB2/genetics ; Receptors, Cannabinoid ; Rimonabant/pharmacology ; Serotonin ; Tics ; Tourette Syndrome
Chemical Substances	Endocannabinoids ; GPR55 protein, mouse ; Receptor, Cannabinoid, CB2 ; Receptors, Cannabinoid ; Serotonin (333DO1RDJY) ; Dronabinol (7J8897W37S) ; ABHD6 protein, human (EC 3.1.1.23) ; Monoacylglycerol Lipases (EC 3.1.1.23) ; Rimonabant (RML78EN3XE)
Language	English
Publishing date	2022-06-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-022-02884-6
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Zs.A 2411: Show issues

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Article ; Online: Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists.

Pertwee, R G

Current medicinal chemistry

2010 Volume 17, Issue 14, Page(s) 1360–1381

Abstract: ... inhibit or block non-CB(1), non- CB(2) G protein-coupled receptors such as GPR55, transmitter gated ...

Abstract	It is widely accepted that non-endogenous compounds that target CB(1) and/or CB(2) receptors possess therapeutic potential for the clinical management of an ever growing number of disorders. Just a few of these disorders are already treated with Delta(9)-tetrahydrocannabinol or nabilone, both CB(1)/CB(2) receptor agonists, and there is now considerable interest in expanding the clinical applications of such agonists and also in exploiting CB(2)-selective agonists, peripherally restricted CB(1)/CB(2) receptor agonists and CB(1)/CB(2) antagonists and inverse agonists as medicines. Already, numerous cannabinoid receptor ligands have been developed and their interactions with CB(1) and CB(2) receptors well characterized. This review describes what is currently known about the ability of such compounds to bind to, activate, inhibit or block non-CB(1), non- CB(2) G protein-coupled receptors such as GPR55, transmitter gated channels, ion channels and nuclear receptors in an orthosteric or allosteric manner. It begins with a brief description of how each of these ligands interacts with CB(1) and/or CB(2) receptors.
MeSH term(s)	Cannabinoid Receptor Agonists ; Cannabinoid Receptor Antagonists ; Dronabinol/analogs & derivatives ; Dronabinol/pharmacology ; Ion Channels/metabolism ; Ligands ; Piperidines/chemistry ; Piperidines/pharmacology ; Pyrazoles/chemistry ; Pyrazoles/pharmacology ; Receptors, Cannabinoid/metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Rimonabant
Chemical Substances	Cannabinoid Receptor Agonists ; Cannabinoid Receptor Antagonists ; Ion Channels ; Ligands ; Piperidines ; Pyrazoles ; Receptors, Cannabinoid ; Receptors, Cytoplasmic and Nuclear ; Receptors, G-Protein-Coupled ; Dronabinol (7J8897W37S) ; Rimonabant (RML78EN3XE)
Language	English
Publishing date	2010-02-17
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1319315-6
ISSN	1875-533X ; 0929-8673
ISSN (online)	1875-533X
ISSN	0929-8673
DOI	10.2174/092986710790980050
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Article ; Online: Therapeutic Potential of Cannabidiol, Cannabidiolic Acid, and Cannabidiolic Acid Methyl Ester as Treatments for Nausea and Vomiting.

Rock, Erin M / Limebeer, Cheryl L / Pertwee, Roger G / Mechoulam, Raphael / Parker, Linda A

Cannabis and cannabinoid research

2021 Volume 6, Issue 4, Page(s) 266–274

Abstract: Introduction: ...

Abstract	Introduction:
MeSH term(s)	Cannabidiol/therapeutic use ; Cannabinoids/therapeutic use ; Esters ; Humans ; Nausea/chemically induced ; Vomiting/chemically induced
Chemical Substances	Cannabinoids ; Esters ; Cannabidiol (19GBJ60SN5) ; cannabidiolic acid (FJX8O3OJCD)
Language	English
Publishing date	2021-06-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2867624-5
ISSN	2378-8763 ; 2578-5125
ISSN (online)	2378-8763
ISSN	2578-5125
DOI	10.1089/can.2021.0041
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Book: Endocannabinoids

Pertwee, R. G

(Handbook of experimental pharmacology ; v.231)

2015

Author's details	Roger G. Pertwee, editor
Series title	Handbook of experimental pharmacology ; v.231
MeSH term(s)	Endocannabinoids/physiology ; Cannabinoid Receptor Modulators/pharmacology ; Endocannabinoids/pharmacology ; Receptors, Cannabinoid/therapeutic use
Language	English
Size	xii, 475 p. :, ill. (chiefly col.) ;, 24 cm.
Publisher	Springer
Publishing place	Cham ; New York
Document type	Book
ISBN	9783319208244 ; 3319208241
Database	Catalogue of the US National Library of Medicine (NLM)

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Article: The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin.

Pertwee, R G

British journal of pharmacology

2008 Volume 153, Issue 2, Page(s) 199–215

Abstract: Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, (-)-trans-delta9-tetrahydrocannabinol (delta9-THC), (-)- ... ...

Abstract	Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, (-)-trans-delta9-tetrahydrocannabinol (delta9-THC), (-)-cannabidiol (CBD) and (-)-trans-delta9-tetrahydrocannabivarin (delta9-THCV), interact with cannabinoid CB1 and CB2 receptors. Delta9-THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signalling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. CBD displays unexpectedly high potency as an antagonist of CB1/CB2 receptor agonists in CB1- and CB2-expressing cells or tissues, the manner with which it interacts with CB2 receptors providing a possible explanation for its ability to inhibit evoked immune cell migration. Delta9-THCV behaves as a potent CB2 receptor partial agonist in vitro. In contrast, it antagonizes cannabinoid receptor agonists in CB1-expressing tissues. This it does with relatively high potency and in a manner that is both tissue and ligand dependent. Delta9-THCV also interacts with CB1 receptors when administered in vivo, behaving either as a CB1 antagonist or, at higher doses, as a CB1 receptor agonist. Brief mention is also made in this review, first of the production by delta9-THC of pharmacodynamic tolerance, second of current knowledge about the extent to which delta9-THC, CBD and delta9-THCV interact with pharmacological targets other than CB1 or CB2 receptors, and third of actual and potential therapeutic applications for each of these cannabinoids.
MeSH term(s)	Animals ; Cannabidiol/pharmacology ; Dronabinol/analogs & derivatives ; Dronabinol/pharmacology ; Drug Tolerance ; Humans ; Receptor, Cannabinoid, CB1/agonists ; Receptor, Cannabinoid, CB1/antagonists & inhibitors ; Receptor, Cannabinoid, CB1/drug effects ; Receptor, Cannabinoid, CB2/agonists ; Receptor, Cannabinoid, CB2/antagonists & inhibitors ; Receptor, Cannabinoid, CB2/drug effects ; Synaptic Transmission/drug effects
Chemical Substances	Receptor, Cannabinoid, CB1 ; Receptor, Cannabinoid, CB2 ; Cannabidiol (19GBJ60SN5) ; tetrahydrocannabivarin 9 (28172-17-0) ; Dronabinol (7J8897W37S)
Language	English
Publishing date	2008-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1038/sj.bjp.0707442
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Book: Handbook of cannabis

Pertwee, R. G

(Handbooks in psychopharmacology)

2014

Author's details	edited by Roger G. Pertwee
Series title	Handbooks in psychopharmacology
MeSH term(s)	Cannabis ; Medical Marijuana ; Cannabinoids ; Phytotherapy
Language	English
Size	xxiv, 747 pages, 8 unnumbered pages of plates :, illustrations ;, 25 cm
Document type	Book
ISBN	9780199662685 ; 0199662681
Database	Catalogue of the US National Library of Medicine (NLM)

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Article: GPR55: a new member of the cannabinoid receptor clan?

Pertwee, R G

British journal of pharmacology

2007 Volume 152, Issue 7, Page(s) 984–986

Abstract: In this issue of the British Journal of Pharmacology, Ryberg et al. present convincing in vitro evidence that the orphan GPCR, GPR55, is a cannabinoid receptor. GPR55 was activated by a range of plant, synthetic and endogenous cannabinoids and blocked by ...

Abstract	In this issue of the British Journal of Pharmacology, Ryberg et al. present convincing in vitro evidence that the orphan GPCR, GPR55, is a cannabinoid receptor. GPR55 was activated by a range of plant, synthetic and endogenous cannabinoids and blocked by the non-psychoactive phytocannabinoid, cannabidiol. Their experiments have revealed several differences between the pharmacology of GPR55 and the established cannabinoid CB1 and CB2 receptors. For example, the CB1 receptor antagonist, AM251, activated GPR55 and the main psychoactive constituent of cannabis, Delta9-tetrahydrocannabinol, displayed greater efficacy at GPR55 than at CB1 or CB2 receptors. They also compared the distribution of GPR55 and CB1 mRNA in mouse and report that GPR55 couples to Galpha13, that it is activated by virodhamine, palmitoylethanolamide and oleoylethanolamide, and that virodhamine displays relatively high efficacy as a GPR55 agonist. Still to be identified are the main roles played by GPR55 in health and disease and any potential therapeutic benefits of activating or blocking this receptor.
MeSH term(s)	Animals ; Arachidonic Acids/pharmacology ; Cannabinoids ; Dronabinol/pharmacology ; Endocannabinoids ; Ethanolamines ; Humans ; Oleic Acids/pharmacology ; Palmitic Acids/pharmacology ; Piperidines/pharmacology ; Pyrazoles/pharmacology ; Receptors, G-Protein-Coupled/agonists ; Receptors, G-Protein-Coupled/drug effects ; Receptors, G-Protein-Coupled/physiology
Chemical Substances	Arachidonic Acids ; Cannabinoids ; Endocannabinoids ; Ethanolamines ; GPR55 protein, human ; Oleic Acids ; Palmitic Acids ; Piperidines ; Pyrazoles ; Receptors, G-Protein-Coupled ; virodhamine ; oleoylethanolamide (1HI5J9N8E6) ; AM 251 (3I4FA44MAI) ; palmidrol (6R8T1UDM3V) ; Dronabinol (7J8897W37S)
Language	English
Publishing date	2007-09-17
Publishing country	England
Document type	Journal Article ; Review ; Comment
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1038/sj.bjp.0707464
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Article ; Online: Design, synthesis, and pharmacological profiling of cannabinoid 1 receptor allosteric modulators: Preclinical efficacy of C2-group GAT211 congeners for reducing intraocular pressure.

Garai, Sumanta / Schaffer, Peter C / Laprairie, Robert B / Janero, David R / Pertwee, Roger G / Straiker, Alex / Thakur, Ganesh A

Bioorganic & medicinal chemistry

2021 Volume 50, Page(s) 116421

Abstract: Allosteric modulators of cannabinoid 1 receptor (CB1R) show translational promise over orthosteric ligands due to their potential to elicit therapeutic benefit without cannabimimetic side effects. The prototypic 2-phenylindole CB1R allosteric modulator, ... ...

Abstract	Allosteric modulators of cannabinoid 1 receptor (CB1R) show translational promise over orthosteric ligands due to their potential to elicit therapeutic benefit without cannabimimetic side effects. The prototypic 2-phenylindole CB1R allosteric modulator, GAT211 (1), demonstrates preclinical efficacy in various disease models. The limited systematic structure-activity relationship (SAR) data at the C2 position of the indole ring within GAT211 invites the opportunity for further modifications to improve GAT211's pharmacological profile while serving to amplify and variegate this library of therapeutically attractive agents. These considerations prompted this focused SAR study in which we substituted the GAT211 C2-phenyl ring with heteroaromatic substituents. The synthesized GAT211 analogs were then evaluated in vitro as CB1R allosteric modulators in cAMP and β-arrestin2 assays with CP55,940 as the orthosteric ligand. Furan and thiophene rings (15c-f and 15m) were the best-tolerated substituents at the C2 position of GAT211 for engagement with human CB1R (hCB1R). The SAR around the novel ligands reported allowed direct experimental characterization of the interaction profile of that pharmacophore with its binding domain in functional, human CB1R, thus offering guidance for accessing subsequent-generation hCB1R allosteric modulators as potential therapeutics. The most potent analog, 15d, markedly promoted orthosteric ligand binding to hCB1R. Pharmacological profiling in the GTPγS and mouse vas deferens assays demonstrated that 15d behaves as a CB1R agonist-positive allosteric modulator (ago-PAM), as confirmed electrophysiologically in autoptic neurons. In vivo, 15d was efficacious as a topical agent that significantly reduced intraocular pressure (IOP) in the ocular normotensive murine model of glaucoma. Since elevated IOP is a decisive risk factor for glaucoma and attendant vision loss, our data support the proposition that the 2-phenylindole class of CB1R ago-PAMs has therapeutic potential for glaucoma and other diseases where potentiation of CB1R signaling may be therapeutic.
MeSH term(s)	Allosteric Regulation/drug effects ; Cannabinoid Receptor Agonists/chemical synthesis ; Cannabinoid Receptor Agonists/chemistry ; Cannabinoid Receptor Agonists/pharmacology ; Dose-Response Relationship, Drug ; Drug Design ; Humans ; Indoles/chemical synthesis ; Indoles/chemistry ; Indoles/pharmacology ; Intraocular Pressure/drug effects ; Molecular Structure ; Receptor, Cannabinoid, CB1/agonists ; Receptor, Cannabinoid, CB1/metabolism ; Structure-Activity Relationship
Chemical Substances	3-(2-nitro-1-phenylethyl)-2-phenyl-1H-indole ; Cannabinoid Receptor Agonists ; Indoles ; Receptor, Cannabinoid, CB1
Language	English
Publishing date	2021-09-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1161284-8
ISSN	1464-3391 ; 0968-0896
ISSN (online)	1464-3391
ISSN	0968-0896
DOI	10.1016/j.bmc.2021.116421
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Article: Pharmacological actions of cannabinoids.

Pertwee, R G

Handbook of experimental pharmacology

2006 , Issue 168, Page(s) 1–51

Abstract: ... at sympathetic nerve terminals, for novel G protein-coupled receptors for R-(+)-WIN55212 and anandamide ... Mammalian tissues express at least two types of cannabinoid receptor, CB1 and CB2, both G protein ...

Abstract	Mammalian tissues express at least two types of cannabinoid receptor, CB1 and CB2, both G protein coupled. CB1 receptors are expressed predominantly at nerve terminals where they mediate inhibition of transmitter release. CB2 receptors are found mainly on immune cells, one of their roles being to modulate cytokine release. Endogenous ligands for these receptors (endocannabinoids) also exist. These are all eicosanoids; prominent examples include arachidonoylethanolamide (anandamide) and 2-arachidonoyl glycerol. These discoveries have led to the development of CB1- and CB2-selective agonists and antagonists and of bioassays for characterizing such ligands. Cannabinoid receptor antagonists include the CB1-selective SR141716A, AM251, AM281 and LY320135, and the CB2-selective SR144528 and AM630. These all behave as inverse agonists, one indication that CB1 and CB2 receptors can exist in a constitutively active state. Neutral cannabinoid receptor antagonists that seem to lack inverse agonist properties have recently also been developed. As well as acting on CB1 and CB2 receptors, there is convincing evidence that anandamide can activate transient receptor potential vanilloid type 1 (TRPV1) receptors. Certain cannabinoids also appear to have non-CB1, non-CB2, non-TRPV1 targets, for example CB2-like receptors that can mediate antinociception and "abnormal-cannabidiol" receptors that mediate vasorelaxation and promote microglial cell migration. There is evidence too for TRPV1-like receptors on glutamatergic neurons, for alpha2-adrenoceptor-like (imidazoline) receptors at sympathetic nerve terminals, for novel G protein-coupled receptors for R-(+)-WIN55212 and anandamide in the brain and spinal cord, for novel receptors for delta9-tetrahydrocannabinol and cannabinol on perivascular sensory nerves and for novel anandamide receptors in the gastro-intestinal tract. The presence of allosteric sites for cannabinoids on various ion channels and non-cannabinoid receptors has also been proposed. In addition, more information is beginning to emerge about the pharmacological actions of the non-psychoactive plant cannabinoid, cannabidiol. These recent advances in cannabinoid pharmacology are all discussed in this review.
MeSH term(s)	Animals ; Biological Assay ; Cannabinoids/pharmacology ; Humans ; Ligands ; Receptor, Cannabinoid, CB1/classification ; Receptor, Cannabinoid, CB1/drug effects ; Receptor, Cannabinoid, CB1/physiology ; Receptor, Cannabinoid, CB2/drug effects ; Receptor, Cannabinoid, CB2/physiology ; TRPV Cation Channels/drug effects ; TRPV Cation Channels/physiology
Chemical Substances	Cannabinoids ; Ligands ; Receptor, Cannabinoid, CB1 ; Receptor, Cannabinoid, CB2 ; TRPV Cation Channels ; TRPV1 receptor
Language	English
Publishing date	2006-03-28
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	0171-2004
ISSN	0171-2004
DOI	10.1007/3-540-26573-2_1
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Article: The pharmacology of cannabinoid receptors and their ligands: an overview.

Pertwee, R G

International journal of obesity (2005)

2006 Volume 30 Suppl 1, Page(s) S13–8

Abstract: Mammalian tissues express at least two cannabinoid receptor types, CB1 and CB2, both G protein ...

Abstract	Mammalian tissues express at least two cannabinoid receptor types, CB1 and CB2, both G protein coupled. CB1 receptors are found predominantly at nerve terminals where they mediate inhibition of transmitter release. CB2 receptors occur mainly on immune cells, one of their roles being to modulate cytokine release. Endogenous agonists for cannabinoid receptors also exist, and are all eicosanoids. The first-discovered of these 'endocannabinoids' was arachidonoylethanolamide and there is convincing evidence that this ligand and some of its metabolites can activate vanilloid VRI (TRPV1) receptors. Certain cannabinoids also appear to have TRPV1-like and/or non-CB1, non-CB2, non-TRPV1 targets. Several CB1- and CB2-selective agonists and antagonists have been developed. Antagonists include the CB1-selective SR141716A, AM251, AM281 and LY320135, and the CB2-selective SR144528 and AM630. These all behave as inverse agonists, one indication that CB1 and CB2 receptors can exist in a constitutively active state. 'Neutral' cannabinoid receptor antagonists have also been developed. CB1 and/or CB2 receptor activation appears to ameliorate inflammatory and neuropathic pain and certain multiple sclerosis symptoms. This might be exploited clinically by using CB1, CB2 or CB1/CB2 agonists, or inhibitors of the membrane transport or catabolism of endocannabinoids that are released in increased amounts, at least in animal models of pain and multiple sclerosis. We have recently discovered the presence of an allosteric site on the CB1 receptor. Consequently, it may also prove possible to enhance 'autoprotective' effects of released endocannabinoids with CB1 allosteric enhancers or, indeed, to reduce proposed 'autoimpairing' effects of released endocannabinoids such as excessive food intake with CB1 allosteric antagonists.
MeSH term(s)	Animals ; Cannabinoid Receptor Agonists ; Cannabinoid Receptor Antagonists ; Cannabinoid Receptor Modulators/metabolism ; Humans ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/metabolism ; Nerve Endings/metabolism ; Pain/drug therapy ; Pain/metabolism ; Receptor, Cannabinoid, CB1/agonists ; Receptor, Cannabinoid, CB1/antagonists & inhibitors ; Receptor, Cannabinoid, CB2/agonists ; Receptor, Cannabinoid, CB2/antagonists & inhibitors ; Receptors, Cannabinoid/metabolism
Chemical Substances	Cannabinoid Receptor Agonists ; Cannabinoid Receptor Antagonists ; Cannabinoid Receptor Modulators ; Receptor, Cannabinoid, CB1 ; Receptor, Cannabinoid, CB2 ; Receptors, Cannabinoid
Language	English
Publishing date	2006-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	752409-2
ISSN	1476-5497 ; 0307-0565
ISSN (online)	1476-5497
ISSN	0307-0565
DOI	10.1038/sj.ijo.0803272
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