Cannabigerol
Minor cannabinoid
Cannabigerol Other names CBG ATC code Legal status
2-[(2E )-3,7-Dimethylocta-2,6-dienyl]-5-pentyl-benzene-1,3-diol
CAS Number PubChem CID IUPHAR/BPS DrugBank ChemSpider UNII KEGG ChEBI ChEMBL CompTox Dashboard (EPA ) ECHA InfoCard 100.346.098 Formula C 21 H 32 O 2 Molar mass 316.485 g·mol−1 3D model (JSmol )
Oc1cc(cc(O)c1C/C=C(\C)CC\C=C(/C)C)CCCCC
InChI=1S/C21H32O2/c1-5-6-7-11-18-14-20(22)19(21(23)15-18)13-12-17(4)10-8-9-16(2)3/h9,12,14-15,22-23H,5-8,10-11,13H2,1-4H3/b17-12+
Y Key:QXACEHWTBCFNSA-SFQUDFHCSA-N
Y
(verify)
Cannabigerol (CBG ) is a non-psychoactive cannabinoid and minor constituent of cannabis .[ 1] [ 2] [ 3] [ 4] [ 5] It is one of more than 120 identified cannabinoids found in the plant genus Cannabis .[ 6] [ 7] The compound is the decarboxylated form of cannabigerolic acid (CBGA), the parent molecule from which other cannabinoids are biosynthesized .[ 2] [ 8]
During plant growth, most of the CBG is converted into other cannabinoids, primarily tetrahydrocannabinol (THC) or cannabidiol (CBD), leaving about 1% CBG in the plant.[ 9] Some strains , however, produce larger amounts of CBG and CBGA, while having low quantities of other cannabinoids, like THC and CBD.[ 10]
The pharmacodynamics of CBG are complex.[ 1] [ 2] [ 3] It is a relatively weak ligand of the cannabinoid receptors , where it acts as a weak partial agonist .[ 1] [ 2] [ 3] [ 11] Conversely, it is a much more potent agonist of the α2 -adrenergic receptor , antagonist of the serotonin 5-HT1A receptor , and antagonist of the transient receptor potential channel TRPM8 .[ 1] [ 2] [ 3] [ 11] CBG also has a variety of other actions that may additionally contribute to its effects.[ 1] [ 2] [ 3] [ 5]
Although CBG is sold as a dietary supplement , its effects and safety for human consumption are unknown.[ 2] Safety concerns have been raised due to the potent activation of α2 -adrenergic receptors by CBG, which may produce sedation and potentially undesirable cardiovascular effects like decreased heart rate and blood pressure .[ 2]
Pharmacology
Pharmacodynamics
CBG lacks psychoactive , cannabimimetic , or psychotropic effects.[ 1] [ 2] [ 3] [ 5] It has been reported to reduce the psychotropic effects of tetrahydrocannabinol (THC).[ 1] The compound has analgesic effects.[ 3] [ 12] [ 13] Preclinical research has also found that CBG reduces intraocular pressure , has antioxidant , anti-inflammatory , anti-tumoral , antibacterial , and antifungal activities, and has antidepressant -like, anxiolytic , neuromodulatory , neuroprotective , dermatological , pro-nausea , and appetite-stimulating effects, among others.[ 1] [ 11] [ 5] [ 12]
CBG has many identified pharmacodynamic actions and its mechanism of action appears to be from interactions with multiple targets .[ 1] [ 2] [ 3]
CBG is a weak ligand of the cannabinoid CB1 and CB2 receptors with affinities (Ki ) of 380–2,600 nM and 153–3,460 nM, respectively.[ 1] [ 2] [ 12] [ 14] [ 15] It is a weak partial agonist or antagonist of both of these receptors.[ 1] [ 2] [ 3] There is no information on the binding or activity of CBG at the GPR55 (the potential non-homologous CB3 receptor).[ 2] [ 3] CBG has relatively low affinity for the cannabinoid receptors, with approximately 5-fold lower affinity for the CB1 receptor and 27-fold lower affinity for the CB2 receptor than THC.[ 11] The low affinity of CBG for the CB1 receptor may in part be involved in its lack of psychoactivity.[ 11]
CBG is a highly potent agonist of the α2 -adrenergic receptor (EC50 Tooltip half-maximal effective concentration = 0.2–72.8 nM) and a moderately potent antagonist of the serotonin 5-HT1A receptor (KB = 51.9 nM).[ 2] [ 1] [ 16] Activation of the α2 -adrenergic receptor by CBG might produce effects including sedation , dry mouth , and decreased heart rate and blood pressure .[ 2] This has raised safety concerns about CBG.[ 2] The actions of CBG at the α2 -adrenergic receptor and 5-HT1A receptor are of far greater potency than its interactions with the cannabinoid receptors and are more likely to be involved in its pharmacodynamic effects.[ 11] These activities may specifically contribute to the analgesic and pro-nausea effects of CBG.[ 12]
The compound is a weak agonist of the transient receptor potential channels TRPA1 (EC50 = 700 nM), TRPV1 (EC50 = 1,300 nM), TRPV2 (EC50 = 1,720 nM), TRPV3 (EC50 = 1,000 nM), and TRPV4 (EC50 = 5,100 nM) (efficacy 18–100% at these targets) and a more potent antagonist of the transient receptor potential channel TRPM8 (IC50 Tooltip half-maximal inhibitory concentration = 160 nM).[ 12] [ 2] [ 1] [ 14] [ 3] It is also a weak agonist of the peroxisome proliferator-activated receptor PPAR-γ (EC50 = 1,270–15,700 nM).[ 2] [ 1] [ 14]
CBG is a voltage-gated sodium channel (VGSC) blocker (Nav 1.1 , Nav 1.2 , Nav 1.5 , and Nav 1.7 ) and voltage-dependent calcium channel (VDCC) blocker.[ 3] [ 1] [ 17] Inhibition of VGSCs may be involved in the analgesic effects of CBG.[ 3]
It shows no inhibition of several endocannabinoid -metabolizing enzymes including fatty acid amide hydrolase (FAAH), diacylglycerol lipase (DGL), and N -acylethanolamine acid amide hydrolase (NAAA).[ 14] However, other research has found that CBG does inhibit FAAH and DGL, as well as monoacylglycerol lipase (MAGL), although it is less potent as an inhibitor of FAAH than cannabidiol (CBD).[ 11] Aside from endocannabinoid-metabolizing enzymes, CBG is a weak inhibitor of the cyclooxygenase COX-1 and COX-2 enzymes (30% inhibition of each at 25,000 nM).[ 1] [ 11] In addition, it has been found to inhibit both the metabolism and reuptake of anandamide .[ 1]
Pharmacokinetics
The pharmacokinetics of CBG have been studied in animals and to a lesser extent in humans.[ 1] [ 11] CBG is metabolized in the liver by CYP2J2 , similarly to other cannabinoids as well as endocannabinoids .[ 1]
Chemistry
CBG is a highly lipophilic and hydrophobic compound.[ 3] Its predicted log P ranges from 7.0 to 7.5.[ 8] [ 18] [ 19]
Synthetic derivatives of CBG have been synthesized and studied.[ 1] [ 11]
History
CBG was isolated from cannabis in 1964.[ 5]
Society and culture
Legal status
CBG is not scheduled by the United Nations Convention on Psychotropic Substances .[citation needed ] In the United States, CBG derived from marijuana is illegal under the Controlled Substances Act , while CBG derived from hemp is legal, as long as the hemp THC content is less than 0.3% of dry weight.[ 20] [ 21]
In Switzerland , it is legal to produce hemp rich in CBG as a tobacco substitute, as long as its THC content remains below 1.0%.[ 22]
Regulation
As of 2022, the US Food and Drug Administration has issued numerous warning letters to American companies for illegally marketing cannabis supplement products,[ 20] including one selling CBG products with unproven illegal claims of efficacy against the COVID-19 virus and inflammation .[ 23]
Biosynthesis
Biosynthesis of CBG.
The biosynthesis of CBG begins by loading hexanoyl-CoA onto a polyketide synthase assembly protein and subsequent condensation with three molecules of malonyl-CoA .[ 24] This polyketide is cyclized to olivetolic acid via olivetolic acid cyclase , and then prenylated with a ten carbon isoprenoid precursor, geranyl pyrophosphate , using an aromatic prenyltransferase enzyme, geranyl-pyrophosphate—olivetolic acid geranyltransferase , to biosynthesize cannabigerolic acid , which can then be decarboxylated to yield CBG.[ 2] [ 4]
Research
CBG is under laboratory research to determine its pharmacological properties and potential effects in disease conditions, with no conclusions about therapeutic effects or safety, as of 2021.[ 2] [ 15] [ 25] A clinical trial published in July 2024 assessed the effects of CBG on anxiety , stress , and mood .[ 26] [ 27]
References
^ a b c d e f g h i j k l m n o p q r s t Calapai F, Cardia L, Esposito E, Ammendolia I, Mondello C, Lo Giudice R, Gangemi S, Calapai G, Mannucci C (2022). "Pharmacological Aspects and Biological Effects of Cannabigerol and Its Synthetic Derivatives" . Evid Based Complement Alternat Med . 2022 : 3336516. doi :10.1155/2022/3336516 . PMC 9666035 . PMID 36397993 .
^ a b c d e f g h i j k l m n o p q r s t Nachnani R, Raup-Konsavage WM, Vrana KE (2021). "The pharmacological case for cannabigerol" . The Journal of Pharmacology and Experimental Therapeutics . 376 (2): 204–212. doi :10.1124/jpet.120.000340 . ISSN 0022-3565 . PMID 33168643 . S2CID 226296897 .
^ a b c d e f g h i j k l m n Ghovanloo MR, Dib-Hajj SD, Goodchild SJ, Ruben PC, Waxman SG (2022). "Non-psychotropic phytocannabinoid interactions with voltage-gated sodium channels: An update on cannabidiol and cannabigerol" . Front Physiol . 13 : 1066455. doi :10.3389/fphys.2022.1066455 . PMC 9691960 . PMID 36439273 .
^ a b Morales P, Reggio PH, Jagerovic N (2017). "An Overview on Medicinal Chemistry of Synthetic and Natural Derivatives of Cannabidiol" . Frontiers in Pharmacology . 8 : 422. doi :10.3389/fphar.2017.00422 . PMC 5487438 . PMID 28701957 .
^ a b c d e Zagožen M, Čerenak A, Kreft S (September 2021). "Cannabigerol and cannabichromene in Cannabis sativa L". Acta Pharm . 71 (3): 355–364. doi :10.2478/acph-2021-0021 . PMID 36654096 .
^ ElSohly MA, Radwan MM, Gul W, Chandra S, Galal A (2017). "Phytochemistry of Cannabis sativa L". Phytochemistry of Cannabis sativa L . Progress in the Chemistry of Organic Natural Products. Vol. 103. pp. 1–36. doi :10.1007/978-3-319-45541-9_1 . ISBN 978-3-319-45539-6 . PMID 28120229 .
^ Turner SE, Williams CM, Iversen L, Whalley BJ (2017). "Molecular Pharmacology of Phytocannabinoids". Phytocannabinoids . Progress in the Chemistry of Organic Natural Products. Vol. 103. pp. 61–101. doi :10.1007/978-3-319-45541-9_3 . ISBN 978-3-319-45539-6 . PMID 28120231 .
^ a b "Cannabigerol; ID 5315659" . PubChem, National Library of Medicine, US National Institutes of Health. 2 July 2022. Retrieved 7 July 2022 .
^ Aizpurua-Olaizola O, Soydaner U, Öztürk E, Schibano D, Simsir Y, Navarro P, et al. (February 2016). "Evolution of the Cannabinoid and Terpene Content during the Growth of Cannabis sativa Plants from Different Chemotypes" . Journal of Natural Products . 79 (2): 324–331. doi :10.1021/acs.jnatprod.5b00949 . PMID 26836472 .
^ Zagožen M, Čerenak A, Kreft S (2021-09-01). "Cannabigerol and cannabichromene in Cannabis sativa L." Acta Pharmaceutica . 71 (3): 355–364. doi :10.2478/acph-2021-0021 . PMID 36654096 . S2CID 231543630 .
^ a b c d e f g h i j Jastrząb A, Jarocka-Karpowicz I, Skrzydlewska E (July 2022). "The Origin and Biomedical Relevance of Cannabigerol" . Int J Mol Sci . 23 (14): 7929. doi :10.3390/ijms23147929 . PMC 9322760 . PMID 35887277 .
^ a b c d e Sampson PB (January 2021). "Phytocannabinoid Pharmacology: Medicinal Properties of Cannabis sativa Constituents Aside from the "Big Two" ". J Nat Prod . 84 (1): 142–160. doi :10.1021/acs.jnatprod.0c00965 . PMID 33356248 .
^ Evans FJ (October 1991). "Cannabinoids: the separation of central from peripheral effects on a structural basis". Planta Med . 57 (7 Suppl): S60–S67. doi :10.1055/s-2006-960231 . PMID 17226225 .
^ a b c d Liu, Tiqing. "BindingDB BDBM50318487 CHEMBL497318::Cannabigerol" . BindingDB . Retrieved 14 August 2024 .
^ a b Morales P, Hurst DP, Reggio PH (2017). "Molecular Targets of the Phytocannabinoids: A Complex Picture". Phytocannabinoids . Progress in the Chemistry of Organic Natural Products. Vol. 103. pp. 103–131. doi :10.1007/978-3-319-45541-9_4 . ISBN 978-3-319-45539-6 . PMC 5345356 . PMID 28120232 .
^ Cascio MG, Gauson LA, Stevenson LA, Ross RA, Pertwee RG (January 2010). "Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist" . Br J Pharmacol . 159 (1): 129–141. doi :10.1111/j.1476-5381.2009.00515.x . PMC 2823359 . PMID 20002104 .
^ Ghovanloo MR, Estacion M, Higerd-Rusli GP, Zhao P, Dib-Hajj S, Waxman SG (August 2022). "Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability". Br J Pharmacol . 179 (15): 4010–4030. doi :10.1111/bph.15833 . PMID 35297036 .
^ "Cannabigerol: Uses, Interactions, Mechanism of Action" . DrugBank Online . 1 February 2019. Retrieved 14 August 2024 .
^ "Cannabigerol" . ChemSpider . 14 August 2024. Retrieved 14 August 2024 .
^ a b "FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)" . US Food and Drug Administration. 21 January 2021. Retrieved 7 July 2022 .
^ "USC > Title 21 > Chapter 13 > Subchapter I > Part A > § 802. Definitions: (16)" (PDF) . Government Publishing Office - US Code . 2016.
^ BAG, Bundesamt für Gesundheit. "Häufig gestellte Fragen (FAQ) zu Tabakersatzprodukten mit THC-armem Hanf mit CBD" . www.bag.admin.ch (in German). Retrieved 2022-07-06 .
^ Ashley D (28 March 2022). "Warning Letter to Greenway Herbal Products LLC; Ref. 627042" . Office of Compliance, Center for Drug Evaluation and Research, Food and Drug Administration. Retrieved 7 July 2022 .
^ Gagne SJ, Stout JM, Liu E, Boubakir Z, Clark SM, Page JE (July 2012). "Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides" . Proceedings of the National Academy of Sciences of the United States of America . 109 (31): 12811–12816. Bibcode :2012PNAS..10912811G . doi :10.1073/pnas.1200330109 . PMC 3411943 . PMID 22802619 .
^ Couch DG, Maudslay H, Doleman B, Lund JN, O'Sullivan SE (March 2018). "The Use of Cannabinoids in Colitis: A Systematic Review and Meta-Analysis" . Inflammatory Bowel Diseases . 24 (4): 680–697. doi :10.1093/ibd/izy014 . PMID 29562280 .
^ Cuttler C, Stueber A, Cooper ZD, Russo E (July 2024). "Acute effects of cannabigerol on anxiety, stress, and mood: a double-blind, placebo-controlled, crossover, field trial" . Sci Rep . 14 (1): 16163. Bibcode :2024NatSR..1416163C . doi :10.1038/s41598-024-66879-0 . PMC 11246434 . PMID 39003387 .
^ "Cannabigerol (CBG) Reduces Anxiety and Improves Memory" . Neuroscience News . 31 July 2024. Retrieved 14 August 2024 .
Phytocannabinoids (comparison )
Cannabibutols Cannabichromenes Cannabicyclols Cannabidiols Cannabielsoins Cannabigerols Cannabiphorols Cannabinols Cannabitriols Cannabivarins Delta-8-tetrahydrocannabinols Delta-9-tetrahydrocannabinols Delta-10-Tetrahydrocannabinols Miscellaneous cannabinoids Active metabolites
Endocannabinoids Synthetic cannabinoid receptor agonists / neocannabinoids
Classical cannabinoids (dibenzopyrans) Non-classical cannabinoids Adamantoylindoles Benzimidazoles Benzoylindoles Cyclohexylphenols Eicosanoids Indazole-3- carboxamides Indole-3-carboxamides Indole-3-carboxylates Naphthoylindazoles Naphthoylindoles Naphthoylpyrroles Naphthylmethylindenes Naphthylmethylindoles Phenylacetylindoles Pyrazolecarboxamides Tetramethylcyclo- propanoylindazoles Tetramethylcyclo- propanoylindoles Others
Allosteric CBR Tooltip Cannabinoid receptor ligands Endocannabinoid enhancers (inactivation inhibitors) Anticannabinoids (antagonists/inverse agonists/antibodies)
α1
Agonists Antagonists
Abanoquil
Ajmalicine
Alfuzosin
Anisodamine
Anisodine
Atiprosin
Atypical antipsychotics (e.g., brexpiprazole , clozapine , olanzapine , quetiapine , risperidone )
Benoxathian
Beta blockers (e.g., adimolol , amosulalol , arotinolol , carvedilol , eugenodilol , labetalol )
Buflomedil
Bunazosin
Corynanthine
Dapiprazole
Domesticine
Doxazosin
Ergolines (e.g., acetergamine , ergotamine , dihydroergotamine , lisuride , nicergoline , terguride )
Etoperidone
Fenspiride
Hydroxyzine
Indoramin
Ketanserin
L-765,314
mCPP
Mepiprazole
Metazosin
Monatepil
Moxisylyte
Naftopidil
Nantenine
Neldazosin
Niaprazine
Niguldipine
Pardoprunox
Pelanserin
Perlapine
Phendioxan
Phenoxybenzamine
Phentolamine
Phenylpiperazine antidepressants (e.g., hydroxynefazodone , nefazodone , trazodone , triazoledione )
Piperoxan
Prazosin
Quinazosin
Quinidine
Silodosin
Spegatrine
Spiperone
Talipexole
Tamsulosin
Terazosin
Tiodazosin
Tolazoline
Tetracyclic antidepressants (e.g., amoxapine , maprotiline , mianserin )
Tricyclic antidepressants (e.g., amitriptyline , clomipramine , doxepin , imipramine , trimipramine )
Trimazosin
Typical antipsychotics (e.g., chlorpromazine , fluphenazine , loxapine , thioridazine )
Urapidil
WB-4101
Zolertine
α2
Agonists Antagonists
1-PP
Adimolol
Amesergide
Aptazapine
Atipamezole
Atypical antipsychotics (e.g., asenapine , brexpiprazole , clozapine , lurasidone , olanzapine , paliperidone , quetiapine , risperidone , zotepine )
Azapirones (e.g., buspirone , gepirone , ipsapirone , tandospirone )
BRL-44408
Buflomedil
Cirazoline
Efaroxan
Esmirtazapine
Fenmetozole
Fluparoxan
Idazoxan
Ketanserin
Lisuride
mCPP
Mianserin
Mirtazapine
NAN-190
Pardoprunox
Phentolamine
Phenoxybenzamine
Piperoxan
Piribedil
Rauwolscine
Rotigotine
Setiptiline
Spegatrine
Spiroxatrine
Sunepitron
Terguride
Tolazoline
Typical antipsychotics (e.g., chlorpromazine , fluphenazine , loxapine , thioridazine )
Yohimbine
β
Receptor (ligands )
CB1 Tooltip Cannabinoid receptor type 1
Agonists(abridged,full list ) Inverse agonists Antagonists
CB2 Tooltip Cannabinoid receptor type 2
Agonists
2-AG
2-AGE (noladin ether)
3,3'-Diindolylmethane
4-O-Methylhonokiol
α-Amyrin · β-Amyrin
A-796,260
A-834,735
A-836,339
AM-1172
AM-1221
AM-1235
AM-1241
AM-2232
Anandamide
AZ-11713908
Cannabinol
Caryophyllene
CB-13
CBS-0550
CP 55,940
GW-405,833 (L-768,242)
GW-842,166X
HU-308
JTE 7-31
JWH-007
JWH-015
JWH-018
JWH-73
JWH-133
L-759,633
L-759,656
Lenabasum (anabasum)
Magnolol
MDA-19
Nabitan
NADA
Olorinab (APD-371)
PF-03550096
S-444,823
SER-601
Serinolamide A
UR-144
Tedalinab
THC (dronabinol)
THCV
Tetrahydromagnolol
Virodhamine
Antagonists
NAGly (GPR18 )
GPR55
GPR119
Transporter (modulators )
eCBTs Tooltip Endocannabinoid transporter
Enzyme (modulators )
Others
Others: 2-PG (directly potentiates activity of 2-AG at CB1 receptor)
ARN-272 (FAAH-like anandamide transporter inhibitor)
Calcium
VDCCs Tooltip Voltage-dependent calcium channels
Potassium
VGKCs Tooltip Voltage-gated potassium channels
IRKs Tooltip Inwardly rectifying potassium channel
KCa Tooltip Calcium-activated potassium channel
K2Ps Tooltip Tandem pore domain potassium channel
Sodium
VGSCs Tooltip Voltage-gated sodium channels
ENaC Tooltip Epithelial sodium channel
ASICs Tooltip Acid-sensing ion channel
Chloride
CaCCs Tooltip Calcium-activated chloride channel
CFTR Tooltip Cystic fibrosis transmembrane conductance regulator
Unsorted
Others
TRPs Tooltip Transient receptor potential channels LGICs Tooltip Ligand gated ion channels
PPARα Tooltip Peroxisome proliferator-activated receptor alpha PPARδ Tooltip Peroxisome proliferator-activated receptor delta PPARγ Tooltip Peroxisome proliferator-activated receptor gamma Non-selective
5-HT1
5-HT1A
Agonists: 8-OH-DPAT
Adatanserin
Amphetamine
Antidepressants (e.g., etoperidone , hydroxynefazodone , nefazodone , trazodone , triazoledione , vilazodone , vortioxetine )
Atypical antipsychotics (e.g., aripiprazole , asenapine , brexpiprazole , cariprazine , clozapine , lurasidone , quetiapine , ziprasidone )
Azapirones (e.g., buspirone , eptapirone , gepirone , perospirone , tandospirone )
Bay R 1531
Befiradol
BMY-14802
Cannabidiol
Dimemebfe
Dopamine
Ebalzotan
Eltoprazine
Enciprazine
Ergolines (e.g., bromocriptine , cabergoline , dihydroergotamine , ergotamine , lisuride , LSD , methylergometrine (methylergonovine) , methysergide , pergolide )
F-11,461
F-12826
F-13714
F-14679
F-15063
F-15,599
Flesinoxan
Flibanserin
Flumexadol
Hypidone
Lesopitron
LY-293284
LY-301317
mCPP
MKC-242
Naluzotan
NBUMP
Osemozotan
Oxaflozane
Pardoprunox
Piclozotan
Rauwolscine
Repinotan
Roxindole
RU-24,969
S-14,506
S-14671
S-15535
Sarizotan
Serotonin (5-HT)
SSR-181507
Sunepitron
Tryptamines (e.g., 5-CT , 5-MeO-DMT , 5-MT , bufotenin , DMT , indorenate , N-Me-5-HT , psilocin , psilocybin )
TGBA01AD
U-92,016-A
Urapidil
Vilazodone
Xaliproden
Yohimbine
Antagonists: Atypical antipsychotics (e.g., iloperidone , risperidone , sertindole )
AV965
Beta blockers (e.g., alprenolol , carteolol , cyanopindolol , iodocyanopindolol , isamoltane , oxprenolol , penbutolol , pindobind , pindolol , propranolol , tertatolol )
BMY-7,378
CSP-2503
Dotarizine
Ergolines (e.g., metergoline )
FCE-24379
Flopropione
GR-46611
Isamoltane
Lecozotan
Mefway
Metitepine (methiothepin)
MIN-117 (WF-516)
MPPF
NAN-190
Robalzotan
S-15535
SB-649,915
SDZ 216-525
Spiperone
Spiramide
Spiroxatrine
UH-301
WAY-100135
WAY-100635
Xylamidine
5-HT1B
Agonists: Anpirtoline
CGS-12066A
CP-93129
CP-94253
CP-122,288
CP-135807
Eltoprazine
Ergolines (e.g., bromocriptine , dihydroergotamine , ergotamine , methylergometrine (methylergonovine) , methysergide , pergolide )
mCPP
RU-24,969
Serotonin (5-HT)
Triptans (e.g., avitriptan , donitriptan , eletriptan , sumatriptan , zolmitriptan )
TFMPP
Tryptamines (e.g., 5-BT , 5-CT , 5-MT , DMT )
Vortioxetine
5-HT1D
Agonists: CP-122,288
CP-135807
CP-286601
Ergolines (e.g., bromocriptine , cabergoline , dihydroergotamine , ergotamine , LSD , methysergide )
GR-46611
L-694247
L-772405
mCPP
PNU-109291
PNU-142633
Serotonin (5-HT)
TGBA01AD
Triptans (e.g., almotriptan , avitriptan , donitriptan , eletriptan , frovatriptan , naratriptan , rizatriptan , sumatriptan , zolmitriptan )
Tryptamines (e.g., 5-BT , 5-CT , 5-Et-DMT , 5-MT , 5-(nonyloxy)tryptamine , DMT )
5-HT1E
5-HT1F
5-HT2
5-HT2A
Agonists: 25H/NB series (e.g., 25I-NBF , 25I-NBMD , 25I-NBOH , 25I-NBOMe , 25B-NBOMe , 25C-NBOMe , 25TFM-NBOMe , 2CBCB-NBOMe , 25CN-NBOH , 2CBFly-NBOMe )
2Cs (e.g., 2C-B , 2C-E , 2C-I , 2C-T-2 , 2C-T-7 , 2C-T-21 )
2C-B-FLY
2CB-Ind
5-Methoxytryptamines (5-MeO-DET , 5-MeO-DiPT , 5-MeO-DMT , 5-MeO-DPT , 5-MT )
α-Alkyltryptamines (e.g., 5-Cl-αMT , 5-Fl-αMT , 5-MeO-αET , 5-MeO-αMT , α-Me-5-HT , αET , αMT )
AL-34662
AL-37350A
Bromo-DragonFLY
Dimemebfe
DMBMPP
DOx (e.g., DOB , DOC , DOI , DOM )
Efavirenz
Ergolines (e.g., 1P-LSD , ALD-52 , bromocriptine , cabergoline , ergine (LSA) , ergometrine (ergonovine) , ergotamine , lisuride , LA-SS-Az , LSB , LSD , LSD-Pip , LSH , LSP , methylergometrine (methylergonovine) , pergolide )
Flumexadol
IHCH-7113
Jimscaline
Lorcaserin
MDxx (e.g., MDA (tenamfetamine) , MDMA (midomafetamine) , MDOH , MMDA )
O-4310
Oxaflozane
PHA-57378
PNU-22394
PNU-181731
RH-34
SCHEMBL5334361
Phenethylamines (e.g., lophophine , mescaline )
Piperazines (e.g., BZP , quipazine , TFMPP )
Serotonin (5-HT)
TCB-2
TFMFly
Tryptamines (e.g., 5-BT , 5-CT , bufotenin , DET , DiPT , DMT , DPT , psilocin , psilocybin , tryptamine )
Antagonists: 5-I-R91150
5-MeO-NBpBrT
AC-90179
Adatanserin
Altanserin
Antihistamines (e.g., cyproheptadine , hydroxyzine , ketotifen , perlapine )
AMDA
Atypical antipsychotics (e.g., amperozide , aripiprazole , asenapine , blonanserin , brexpiprazole , carpipramine , clocapramine , clorotepine , clozapine , fluperlapine , gevotroline , iloperidone , lurasidone , melperone , mosapramine , ocaperidone , olanzapine , paliperidone , quetiapine , risperidone , sertindole , zicronapine , ziprasidone , zotepine )
Chlorprothixene
Cinanserin
CSP-2503
Deramciclane
Dotarizine
Eplivanserin
Ergolines (e.g., amesergide , LY-53857 , LY-215,840 , mesulergine , metergoline , methysergide , sergolexole )
Fananserin
Flibanserin
Glemanserin
Irindalone
Ketanserin
KML-010
Landipirdine
LY-393558
mCPP
Medifoxamine
Metitepine (methiothepin)
MIN-117 (WF-516)
Naftidrofuryl
Nantenine
Nelotanserin
Opiranserin (VVZ-149)
Pelanserin
Phenoxybenzamine
Pimavanserin
Pirenperone
Pizotifen
Pruvanserin
Rauwolscine
Ritanserin
Roluperidone
S-14671
Sarpogrelate
Serotonin antagonists and reuptake inhibitors (e.g., etoperidone , hydroxynefazodone , lubazodone , mepiprazole , nefazodone , triazoledione , trazodone )
SR-46349B
TGBA01AD
Teniloxazine
Temanogrel
Tetracyclic antidepressants (e.g., amoxapine , aptazapine , esmirtazapine , maprotiline , mianserin , mirtazapine )
Tricyclic antidepressants (e.g., amitriptyline )
Typical antipsychotics (e.g., chlorpromazine , fluphenazine , haloperidol , loxapine , perphenazine , pimozide , pipamperone , prochlorperazine , setoperone , spiperone , spiramide , thioridazine , thiothixene , trifluoperazine )
Volinanserin
Xylamidine
Yohimbine
5-HT2B
Agonists: 4-Methylaminorex
Aminorex
Amphetamines (e.g., chlorphentermine , cloforex , dexfenfluramine , fenfluramine , levofenfluramine , norfenfluramine )
BW-723C86
DOx (e.g., DOB , DOC , DOI , DOM )
Ergolines (e.g., cabergoline , dihydroergocryptine , dihydroergotamine , ergotamine , methylergometrine (methylergonovine) , methysergide , pergolide )
Lorcaserin
MDxx (e.g., MDA (tenamfetamine) , MDMA (midomafetamine) , MDOH , MMDA )
Piperazines (e.g., TFMPP )
PNU-22394
Ro60-0175
Serotonin (5-HT)
Tryptamines (e.g., 5-BT , 5-CT , 5-MT , α-Me-5-HT , bufotenin , DET , DiPT , DMT , DPT , psilocin , psilocybin , tryptamine )
Antagonists: Agomelatine
Atypical antipsychotics (e.g., amisulpride , aripiprazole , asenapine , brexpiprazole , cariprazine , clozapine , N-desalkylquetiapine (norquetiapine) , N-desmethylclozapine (norclozapine) , olanzapine , pipamperone , quetiapine , risperidone , ziprasidone )
Cyproheptadine
EGIS-7625
Ergolines (e.g., amesergide , bromocriptine , lisuride , LY-53857 , LY-272015 , mesulergine )
Ketanserin
LY-393558
mCPP
Metadoxine
Metitepine (methiothepin)
Pirenperone
Pizotifen
Propranolol
PRX-08066
Rauwolscine
Ritanserin
RS-127445
Sarpogrelate
SB-200646
SB-204741
SB-206553
SB-215505
SB-221284
SB-228357
SDZ SER-082
Tegaserod
Tetracyclic antidepressants (e.g., amoxapine , mianserin , mirtazapine )
Trazodone
Typical antipsychotics (e.g., chlorpromazine )
TIK-301
Yohimbine
5-HT2C
Agonists: 2Cs (e.g., 2C-B , 2C-E , 2C-I , 2C-T-2 , 2C-T-7 , 2C-T-21 )
5-Methoxytryptamines (5-MeO-DET , 5-MeO-DiPT , 5-MeO-DMT , 5-MeO-DPT , 5-MT )
α-Alkyltryptamines (e.g., 5-Cl-αMT , 5-Fl-αMT , 5-MeO-αET , 5-MeO-αMT , α-Me-5-HT , αET , αMT )
A-372159
AL-38022A
Alstonine
CP-809101
Dimemebfe
DOx (e.g., DOB , DOC , DOI , DOM )
Ergolines (e.g., ALD-52 , cabergoline , dihydroergotamine , ergine (LSA) , ergotamine , lisuride , LA-SS-Az , LSB , LSD , LSD-Pip , LSH , LSP , pergolide )
Flumexadol
Lorcaserin
MDxx (e.g., MDA (tenamfetamine) , MDMA (midomafetamine) , MDOH , MMDA )
MK-212
ORG-12962
ORG-37684
Oxaflozane
PHA-57378
Phenethylamines (e.g., lophophine , mescaline )
Piperazines (e.g., aripiprazole , BZP , mCPP , quipazine , TFMPP )
PNU-22394
PNU-181731
Ro60-0175
Ro60-0213
Serotonin (5-HT)
Tryptamines (e.g., 5-BT , 5-CT , bufotenin , DET , DiPT , DMT , DPT , psilocin , psilocybin , tryptamine )
Vabicaserin
WAY-629
WAY-161503
YM-348
Antagonists: Adatanserin
Agomelatine
Atypical antipsychotics (e.g., asenapine , clorotepine , clozapine , fluperlapine , iloperidone , melperone , olanzapine , paliperidone , quetiapine , risperidone , sertindole , ziprasidone , zotepine )
Captodiame
CEPC
Cinanserin
Cyproheptadine
Deramciclane
Desmetramadol
Dotarizine
Eltoprazine
Ergolines (e.g., amesergide , bromocriptine , LY-53857 , LY-215,840 , mesulergine , metergoline , methysergide , sergolexole )
Etoperidone
Fluoxetine
FR-260010
Irindalone
Ketanserin
Ketotifen
Latrepirdine (dimebolin)
Medifoxamine
Metitepine (methiothepin)
Nefazodone
Pirenperone
Pizotifen
Propranolol
Ritanserin
RS-102221
S-14671
SB-200646
SB-206553
SB-221284
SB-228357
SB-242084
SB-243213
SDZ SER-082
Tedatioxetine
Tetracyclic antidepressants (e.g., amoxapine , aptazapine , esmirtazapine , maprotiline , mianserin , mirtazapine )
TIK-301
Tramadol
Trazodone
Tricyclic antidepressants (e.g., amitriptyline , nortriptyline )
Typical antipsychotics (e.g., chlorpromazine , loxapine , pimozide , pipamperone , thioridazine )
Xylamidine
5-HT3 –7
5-HT3
Agonists: Alcohols (e.g., butanol , ethanol (alcohol) , trichloroethanol )
m-CPBG
Phenylbiguanide
Piperazines (e.g., BZP , mCPP , quipazine )
RS-56812
Serotonin (5-HT)
SR-57227
SR-57227A
Tryptamines (e.g., 2-Me-5-HT , 5-CT , bufotenidine (5-HTQ) )
Volatiles/gases (e.g., halothane , isoflurane , toluene , trichloroethane )
YM-31636
Antagonists: Alosetron
Anpirtoline
Arazasetron
AS-8112
Atypical antipsychotics (e.g., clozapine , olanzapine , quetiapine )
Azasetron
Batanopride
Bemesetron (MDL-72222)
Bupropion
Cilansetron
CSP-2503
Dazopride
Dolasetron
Galanolactone
Granisetron
Hydroxybupropion
Lerisetron
Memantine
Ondansetron
Palonosetron
Ramosetron
Renzapride
Ricasetron
Tedatioxetine
Tetracyclic antidepressants (e.g., amoxapine , mianserin , mirtazapine )
Thujone
Tropanserin
Tropisetron
Typical antipsychotics (e.g., loxapine )
Volatiles/gases (e.g., nitrous oxide , sevoflurane , xenon )
Vortioxetine
Zacopride
Zatosetron
5-HT4
5-HT5A
5-HT6
Agonists: Ergolines (e.g., dihydroergocryptine , dihydroergotamine , ergotamine , lisuride , LSD , mesulergine , metergoline , methysergide )
Hypidone
Serotonin (5-HT)
Tryptamines (e.g., 2-Me-5-HT , 5-BT , 5-CT , 5-MT , Bufotenin , E-6801 , E-6837 , EMD-386088 , EMDT , LY-586713 , N-Me-5-HT , ST-1936 , tryptamine )
WAY-181187
WAY-208466
Antagonists: ABT-354
Atypical antipsychotics (e.g., aripiprazole , asenapine , clorotepine , clozapine , fluperlapine , iloperidone , olanzapine , tiospirone )
AVN-101
AVN-211
AVN-322
AVN-397
BGC20-760
BVT-5182
BVT-74316
Cerlapirdine
EGIS-12,233
GW-742457
Idalopirdine
Ketanserin
Landipirdine
Latrepirdine (dimebolin)
Masupirdine
Metitepine (methiothepin)
MS-245
PRX-07034
Ritanserin
Ro 04-6790
Ro 63-0563
SB-258585
SB-271046
SB-357134
SB-399885
SB-742457
Tetracyclic antidepressants (e.g., amoxapine , mianserin )
Tricyclic antidepressants (e.g., amitriptyline , clomipramine , doxepin , nortriptyline )
Typical antipsychotics (e.g., chlorpromazine , loxapine )
5-HT7
Antagonists: Atypical antipsychotics (e.g., amisulpride , aripiprazole , asenapine , brexpiprazole , clorotepine , clozapine , fluperlapine , olanzapine , risperidone , sertindole , tiospirone , ziprasidone , zotepine )
Butaclamol
DR-4485
EGIS-12,233
Ergolines (e.g., 2-Br-LSD (BOL-148) , amesergide , bromocriptine , cabergoline , dihydroergotamine , ergotamine , LY-53857 , LY-215,840 , mesulergine , metergoline , methysergide , sergolexole )
JNJ-18038683
Ketanserin
LY-215,840
Metitepine (methiothepin)
Ritanserin
SB-258719
SB-258741
SB-269970
SB-656104
SB-656104A
SB-691673
SLV-313
SLV-314
Spiperone
SSR-181507
Tetracyclic antidepressants (e.g., amoxapine , maprotiline , mianserin , mirtazapine )
Tricyclic antidepressants (e.g., amitriptyline , clomipramine , imipramine )
Typical antipsychotics (e.g., acetophenazine , chlorpromazine , chlorprothixene , fluphenazine , loxapine , pimozide )
Vortioxetine
TRPA
Activators
4-Hydroxynonenal
4-Oxo-2-nonenal
4,5-EET
12S-HpETE
15-Deoxy-Δ12,14 -prostaglandin J2
α-Sanshool (ginger , Sichuan and melegueta peppers )
Acrolein
Allicin (garlic )
Allyl isothiocyanate (mustard , radish , horseradish , wasabi )
AM404
ASP-7663
Bradykinin
Cannabichromene (cannabis )
Cannabidiol (cannabis )
Cannabigerol (cannabis )
Cinnamaldehyde (cinnamon )
CR gas (dibenzoxazepine; DBO)
CS gas (2-chlorobenzal malononitrile)
Cuminaldehyde (cumin )
Curcumin (turmeric )
Dehydroligustilide (celery )
Diallyl disulfide
Dicentrine (Lindera spp.)
Farnesyl thiosalicylic acid
Formalin
Gingerols (ginger )
Hepoxilin A3
Hepoxilin B3
Hydrogen peroxide
Icilin
Isothiocyanate
JT-010
Ligustilide (celery , Angelica acutiloba )
Linalool (Sichuan pepper , thyme )
Methylglyoxal
Methyl salicylate (wintergreen )
N-Methylmaleimide
Nicotine (tobacco )
Oleocanthal (olive oil )
Paclitaxel (Pacific yew )
Paracetamol (acetaminophen)
PF-4840154
Phenacyl chloride
Polygodial (Dorrigo pepper )
Shogaols (ginger , Sichuan and melegueta peppers )
Tear gases
Tetrahydrocannabinol (cannabis )
Tetrahydrocannabiorcol
Thiopropanal S-oxide (onion )
Umbellulone (Umbellularia californica )
WIN 55,212-2
Blockers
TRPC
TRPM
TRPML
TRPP
TRPV
Activators
2-APB
5',6'-EET
9-HODE
9-oxoODE
12S-HETE
12S-HpETE
13-HODE
13-oxoODE
20-HETE
α-Sanshool (ginger , Sichuan and melegueta peppers )
Allicin (garlic )
AM404
Anandamide
Bisandrographolide (Andrographis paniculata )
Camphor (camphor laurel , rosemary , camphorweed , African blue basil , camphor basil )
Cannabidiol (cannabis )
Cannabidivarin (cannabis )
Capsaicin (chili pepper )
Carvacrol (oregano , thyme , pepperwort , wild bergamot , others)
DHEA
Diacyl glycerol
Dihydrocapsaicin (chili pepper )
Estradiol
Eugenol (basil , clove )
Evodiamine (Euodia ruticarpa )
Gingerols (ginger )
GSK1016790A
Heat
Hepoxilin A3
Hepoxilin B3
Homocapsaicin (chili pepper )
Homodihydrocapsaicin (chili pepper )
Incensole (incense )
Lysophosphatidic acid
Low pH (acidic conditions)
Menthol (mint )
N-Arachidonoyl dopamine
N-Oleoyldopamine
N-Oleoylethanolamide
Nonivamide (PAVA) (PAVA spray )
Nordihydrocapsaicin (chili pepper )
Paclitaxel (Pacific yew )
Paracetamol (acetaminophen)
Phenylacetylrinvanil
Phorbol esters (e.g., 4α-PDD )
Piperine (black pepper , long pepper )
Polygodial (Dorrigo pepper )
Probenecid
Protons
RhTx
Rutamarin (Ruta graveolens )
Resiniferatoxin (RTX) (Euphorbia resinifera /pooissonii )
Shogaols (ginger , Sichuan and melegueta peppers )
Tetrahydrocannabivarin (cannabis )
Thymol (thyme , oregano )
Tinyatoxin (Euphorbia resinifera /pooissonii )
Tramadol
Vanillin (vanilla )
Zucapsaicin
Blockers