This article is about DHEA sulfate as a hormone. For its use as a medication, see
Prasterone sulfate .
Dehydroepiandrosterone sulfate Names IUPAC name 17-Oxoandrost-5-en-3β-yl hydrogen sulfate
Systematic IUPAC name (3aS ,3bR ,7S ,9aR ,9bS ,11aS )-9a,11a-Dimethyl-1-oxo-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H -cyclopenta[a ]phenanthren-7-yl hydrogen sulfate
Other namesAndrostenolone sulfate; Prasterone sulfate; Androst-5-en-3β-ol-17-one 3β-sulfate
Identifiers Abbreviations DHEA sulfate; DHEA-S; DHEAS ChemSpider UNII InChI=1S/C19H28O5S/c1-18-9-7-13(24-25(21,22)23)11-12(18)3-4-14-15-5-6-17(20)19(15,2)10-8-16(14)18/h3,13-16H,4-11H2,1-2H3,(H,21,22,23)/t13-,14-,15-,16-,18-,19-/m0/s1
N Key: CZWCKYRVOZZJNM-USOAJAOKSA-N
N InChI=1/C19H28O5S/c1-18-9-7-13(24-25(21,22)23)11-12(18)3-4-14-15-5-6-17(20)19(15,2)10-8-16(14)18/h3,13-16H,4-11H2,1-2H3,(H,21,22,23)/t13-,14-,15-,16-,18-,19-/m0/s1
Key: CZWCKYRVOZZJNM-USOAJAOKBK
Properties C19 H28 O5 S Molar mass 368.49 g/mol Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Dehydroepiandrosterone sulfate , abbreviated asDHEA sulfate orDHEA-S , also known asandrostenolone sulfate , is anendogenous androstane steroid that is produced by theadrenal cortex .[ 1] sulfate ester and ametabolite ofdehydroepiandrosterone (DHEA) and circulates in far greater relative concentrations than DHEA.[ 2] hormonally inert and is instead an importantneurosteroid andneurotrophin .[ 2]
Biological activity [ edit ] Neurosteroid activity [ edit ] Similarly to otherconjugated steroids, DHEA-S is devoid ofhormonal activity, lackingaffinity for thesteroid hormone receptors .[ 3] [ 4] neurosteroid andneurotrophin .[ 2] positive allosteric modulator of theNMDA receptor (50 nM–1 μM),negative allosteric modulator of theGABAA andglycine receptors , and weakagonist of thesigma-1 receptor (Kd > 50 μM).[ 2] [ 5] TrkA andp75NTR – receptors of neurotrophins likenerve growth factor (NGF) andbrain-derived neurotrophic factor (BDNF) – with high affinity (around 5 nM).[ 2] [ 6] [ 7] [ 8]
Although DHEA-S itself is hormonally inert, it has been thought that it can be converted back into DHEA,[ 9] androgenic andestrogenic , and that DHEA in turn can be transformed into more potent androgens liketestosterone anddihydrotestosterone (DHT) as well as estrogens likeestradiol .[ 2] [ 1] [ 10] prohormone with the potential for androgenic and estrogenic effects.[ 2] [ 1] [ 10] [ 11]
DHEA-S has also been found to inhibit theTRPV1 andTRPC5 transient receptor potential channels and to inhibit theP2X receptor .[ 5]
Comprehensive overview ofsteroidogenesis , showing DHEA, the precursor of DHEA-S, at left among the androgens.[ 12] DHEA and DHEA-S are produced in thezona reticularis of theadrenal cortex under the control ofadrenocorticotropic hormone (ACTH).[ 1] cholesterol via theenzymes cholesterol side-chain cleavage enzyme (CYP11A1; P450scc) and17α-hydroxylase/17,20-lyase (CYP17A1), withpregnenolone and17α-hydroxypregnenolone asintermediates .[ 13] sulfation of DHEA at the C3β position via thesulfotransferase enzymes SULT2A1 and to a lesser extentSULT1E1 .[ 13] [ 14] [ 15] gonads (10%),[ 16] [ 1] [ 17] [ 18] [ 19]
Unlike DHEA, which is weakly bound toalbumin , DHEA-S is strongly bound to albumin (i.e., with very high affinity), and this is the reason for its much longer comparativeterminal half-life .[ 20] [ 21] sex hormone-binding globulin (SHBG).[ 22]
Whereas DHEA easily crosses theblood–brain barrier into thecentral nervous system ,[ 23] [ 24]
DHEA-S can be converted back into DHEA viasteroid sulfatase (STS).[ 9] premenopausal women, 40 to 75% of circulating testosterone is derived from peripheralmetabolism of DHEA-S, and inpostmenopausal women, over 90% of estrogens, mainlyestrone , are derived from peripheral metabolism of DHEA-S.[ 2] estradiol .[ 25] depot for potent androgens like testosterone and dihydrotestosterone inprostate cancer , which fuel the growth of this cancer.[ 26]
The elimination half-life of DHEA-S is 7 to 10 hours, which is far longer than that of DHEA, which has an elimination half-life of only 15 to 30 minutes.[ 21]
DHEA-S isexcreted in theurine via thekidneys .[ 27]
DHEA-S levels throughout life in humans.[ 28] DHEA and DHEA-S are the most abundant circulating steroids in the body.[ 29] cortisol , 100 to 500 times those of testosterone, and 1,000 to 10,000 times higher than those of estradiol.[ 30] [ 3]
Levels of DHEA and DHEA-S vary throughout life.[ 2] [ 1] adrenarche around 6 to 8 years of age, at which point they markedly increase,[ 31] [ 2] [ 1] [ 29] [ 29]
DHEA-S levels are higher in men than in women.[ 2] [ 29]
Reference ranges for DHEA-S in females[ 32] Tanner stage and average ageLower limit Upper limit Unit Tanner stage I >14 days 16 96 μg /dLTanner stage II 10.5 years 22 184 Tanner stage III 11.6 years <15 296 Tanner stage IV 12.3 years 17 343 Tanner stage V 14.5 years 44 332 18–29 years 44 332 30–39 years 31 228 40–49 years 18 244 50–59 years <15 200 > or =60 years <15 157
Reference ranges for DHEA-S in males[ 32] Tanner stage and average ageLower limit Upper limit Unit Tanner stage I >14 days <15 120 μg /dLTanner stage II 11.5 years <15 333 Tanner stage III 13.6 years <15 312 Tanner stage IV 15.1 years 29 412 Tanner stage V 18.0 years 89 457 18–29 years 89 457 30–39 years 65 334 40–49 years 48 244 50–59 years 35 179 > or =60 years 25 131
TheEndocrine Society recommends against the therapeutic use of DHEA-S in both healthy women and those withadrenal insufficiency , as its role is not clear from studies performed so far.[ 33] hypopituitarism ,adrenal insufficiency , menopause due to ovarian surgery,glucocorticoid use, or other conditions associated with low androgen levels; this is because there are limited data supporting improvement in signs and symptoms with therapy and no long-term studies of risk.[ 33]
In otherwise elderly women, in whom an age-related fall of DHEA-S may be associated with menopausal symptoms and reduced libido, DHEA-S supplementation cannot currently be said to improve outcomes.[ 34]
As thesodium salt ,prasterone sodium sulfate , DHEA-S is used as apharmaceutical drug inJapan in the treatment of insufficientcervical ripening andcervical dilation duringchildbirth .[ 35] [ 36] [ 37] [ 38] [ 39] [ 40] [ 41]
DHEA-S levels above 1890 μM or 700 to 800 μg/dL are highly suggestive ofadrenal dysfunction because DHEA-S is made by the adrenal glands[ 42] [ 43] [ 44]
Women withhirsutism commonly present with mildly elevated DHEA-S levels.[ 45] etiologies for hirsutism includeovarian dysfunction (polycystic ovary syndrome ) andadrenal dysfunction (congenital adrenal hyperplasia ,cushing's syndrome ,androgen secreting tumors); 90% of these cases are caused byPCOS or areidiopathic in nature.[ 45] [ 45]
DHEA-S, also known as androst-5-en-3β-ol-17-one 3β-sulfate, is anaturally occurring androstane steroid and the C3βsulfate ester of DHEA.
^a b c d e f g Risto Erkkola (2006).The Menopause ISBN 978-0-444-51830-9 ^a b c d e f g h i j k Prough RA, Clark BJ, Klinge CM (2016)."Novel mechanisms for DHEA action" .J. Mol. Endocrinol .56 (3): R139–55.doi :10.1530/JME-16-0013 PMID 26908835 . ^a b Walter K.H. Krause (30 November 2008).Cutaneous Manifestations of Endocrine Diseases ISBN 978-3-540-88367-8 Plasma DHEA-S levels in adult men and women are 100-500 times higher than those of testosterone and 1000-10000 times higher than those of estradiol. ^ Mo Q, Lu SF, Simon NG (2006). "Dehydroepiandrosterone and its metabolites: differential effects on androgen receptor trafficking and transcriptional activity".J. Steroid Biochem. Mol. Biol .99 (1):50– 8.doi :10.1016/j.jsbmb.2005.11.011 .PMID 16524719 .S2CID 30489004 . ^a b Steven R. King (9 November 2012).Neurosteroids and the Nervous System ISBN 978-1-4614-5559-2 ^ Lazaridis I, Charalampopoulos I, Alexaki VI, Avlonitis N, Pediaditakis I, Efstathopoulos P, Calogeropoulou T, Castanas E, Gravanis A (2011)."Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis" .PLOS Biol .9 (4): e1001051.doi :10.1371/journal.pbio.1001051 PMC 3082517 PMID 21541365 . ^ Pediaditakis I, Iliopoulos I, Theologidis I, Delivanoglou N, Margioris AN, Charalampopoulos I, Gravanis A (2015)."Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors" .Endocrinology .156 (1):16– 23.doi :10.1210/en.2014-1596 PMID 25330101 . ^ Gravanis A, Calogeropoulou T, Panoutsakopoulou V, Thermos K, Neophytou C, Charalampopoulos I (2012). "Neurosteroids and microneurotrophins signal through NGF receptors to induce prosurvival signaling in neuronal cells".Sci Signal .5 (246): pt8.doi :10.1126/scisignal.2003387 .PMID 23074265 .S2CID 26914550 . ^a b Robert Morfin (2 September 2003).DHEA and the Brain ISBN 978-0-203-30121-0 ^a b Marc A. Fritz; Leon Speroff (28 March 2012).Clinical Gynecologic Endocrinology and Infertility ISBN 978-1-4511-4847-3 ^ Hammer F, Subtil S, Lux P, Maser-Gluth C, Stewart PM, Allolio B, Arlt W (2005). "No evidence for hepatic conversion of dehydroepiandrosterone (DHEA) sulfate to DHEA: in vivo and in vitro studies".J. Clin. Endocrinol. Metab .90 (6):3600– 5.doi :10.1210/jc.2004-2386 .PMID 15755854 . ^ Häggström, Mikael; Richfield, David (2014)."Diagram of the pathways of human steroidogenesis" .WikiJournal of Medicine .1 (1).doi :10.15347/wjm/2014.005 ISSN 2002-4436 . ^a b Rainey WE, Nakamura Y (February 2008)."Regulation of the adrenal androgen biosynthesis" .J. Steroid Biochem. Mol. Biol .108 (3– 5):281– 86.doi :10.1016/j.jsbmb.2007.09.015 .PMC 2699571 PMID 17945481 . ^ Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA (2015)."The Regulation of Steroid Action by Sulfation and Desulfation" .Endocr. Rev .36 (5):526– 63.doi :10.1210/er.2015-1036 .PMC 4591525 PMID 26213785 . ^ Lawrence H Lash (2005).Drug Metabolism and Transport: Molecular Methods and Mechanisms ISBN 978-1-59259-832-8 ^ Wolf-Bernhard Schill; Frank H. Comhaire; Timothy B. Hargreave (26 August 2006).Andrology for the Clinician ISBN 978-3-540-33713-3 ^ Gretchen M. Lentz; Rogerio A. Lobo; David M. Gershenson; Vern L. Katz (2012).Comprehensive Gynecology ISBN 978-0-323-06986-1 ^ Dimitrios A. Linos; Jon A. van Heerden (5 December 2005).Adrenal Glands: Diagnostic Aspects and Surgical Therapy ISBN 978-3-540-26861-1 ^ G.A.W. Rook; S. Lightman (6 December 2012).Steroid Hormones and the T-Cell Cytokine Profile ISBN 978-1-4471-0931-0 ^ Kenneth L. Becker (2001).Principles and Practice of Endocrinology and Metabolism ISBN 978-0-7817-1750-2 ^a b Bruce Alan White; Susan P. Porterfield (2013).Endocrine and Reproductive Physiology, Mosby Physiology Monograph Series (with Student Consult Online Access),4: Endocrine and Reproductive Physiology ISBN 978-0-323-08704-9 ^ Paul M. Coates; M. Coates Paul; Marc Blackman; Marc R. Blackman, Gordon M. Cragg, Mark Levine, Jeffrey D. White, Joel Moss, Mark A. Levine (29 December 2004).Encyclopedia of Dietary Supplements (Print) ISBN 978-0-8247-5504-1 {{cite book }}: CS1 maint: multiple names: authors list (link )^ Joseph E. Pizzorno (2013).Textbook of Natural Medicine ISBN 978-1-4377-2333-5 ^ Samuel S. C. Yen; Robert B. Jaffe; Robert L. Barbieri (January 1999).Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management 40 .ISBN 978-0-7216-6897-0 Thus, the formation of DHEA-S occurs directly in the brain, particularly because DHEA-S does not cross the blood-brain barrier [...] ^ Nguyen AD, Conley AJ (2008). "Adrenal androgens in humans and nonhuman primates: production, zonation and regulation".Endocr Dev . Endocrine Development.13 :33– 54.doi :10.1159/000134765 .ISBN 978-3-8055-8580-4 PMID 18493132 . ^ Penning TM (2018)."Dehydroepiandrosterone (DHEA)-SO4 Depot and Castration-Resistant Prostate Cancer" .Vitam. Horm . Vitamins and Hormones.108 :309– 331.doi :10.1016/bs.vh.2018.01.007 .ISBN 9780128143612 PMC 6226251 PMID 30029732 . ^ S.S. Nussey; S.A. Whitehead (8 April 2013).Endocrinology: An Integrated Approach ISBN 978-0-203-45043-7 ^ Mark A. Sperling (10 April 2014).Pediatric Endocrinology E-Book ISBN 978-1-4557-5973-6 ^a b c d Philip E. Harris; Pierre-Marc G. Bouloux (24 March 2014).Endocrinology in Clinical Practice, Second Edition ISBN 978-1-84184-952-2 ^ Abraham Weizman (1 February 2008).Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment ISBN 978-1-4020-6854-6 ^ Douglas T. Carrell; C. Matthew Peterson (23 March 2010).Reproductive Endocrinology and Infertility: Integrating Modern Clinical and Laboratory Practice ISBN 978-1-4419-1436-1 ^a b Dehydroepiandrosterone Sulfate (DHEA-S), Serum Archived 2018-03-14 at theWayback Machine at Mayo Foundation For Medical Education And Research. Retrieved July 2012^a b Wierman, Margaret E.; Arlt, Wiebke; Basson, Rosemary; Davis, Susan R.; Miller, Karen K.; Murad, Mohammad H.; Rosner, William; Santoro, Nanette (2014)."Androgen Therapy in Women: A Reappraisal: An Endocrine Society Clinical Practice Guideline" .The Journal of Clinical Endocrinology & Metabolism .99 (10):3489– 510.doi :10.1210/jc.2014-2260 PMID 25279570 . ^ Elraiyah, Tarig; Sonbol, Mohamad Bassam; Wang, Zhen; Khairalseed, Tagwa; Asi, Noor; Undavalli, Chaitanya; Nabhan, Mohammad; Altayar, Osama; Prokop, Larry; Montori, Victor M.; Murad, Mohammad Hassan (2014)."The Benefits and Harms of Systemic Dehydroepiandrosterone (DHEA) in Postmenopausal Women With Normal Adrenal Function: A Systematic Review and Meta-analysis" .The Journal of Clinical Endocrinology & Metabolism .99 (10):3536– 42.doi :10.1210/jc.2014-2261 .PMC 5393492 PMID 25279571 . ^ J. Elks (14 November 2014).The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies ISBN 978-1-4757-2085-3 ^ John W. Blunt; Murray H. G. Munro (19 September 2007).Dictionary of Marine Natural Products with CD-ROM ISBN 978-0-8493-8217-8 ^ A. Kleemann; J. Engel; B. Kutscher; D. Reichert (14 May 2014).Pharmaceutical Substances, 5th Edition, 2009: Syntheses, Patents and Applications of the most relevant APIs 2441– 2442.ISBN 978-3-13-179525-0 ^ Martin Negwer; Hans-Georg Scharnow (2001).Organic-chemical drugs and their synonyms: (an international survey) ISBN 978-3-527-30247-5 3β-Hydroxyandrost-5-en-17-one hydrogen sulfate = (3β)-3-(Sulfooxy)androst-5-en-17-one. R: Sodium salt (1099-87-2). S: Astenile, Dehydroepiandrosterone sulfate sodium, DHA-S, DHEAS, KYH 3102, Mylis, PB 005, Prasterone sodium sulfate, Teloin ^ Jianqiu Y (1992). "Clinical Application of Prasterone Sodium Sulfate".Chinese Journal of New Drugs .5 : 015. ^ Sakaguchi M, Sakai T, Adachi Y, Kawashima T, Awata N (1992)."The biological fate of sodium prasterone sulfate after vaginal administration. I. Absorption and excretion in rats" .J. Pharmacobio-Dyn .15 (2):67– 73.doi :10.1248/bpb1978.15.67 PMID 1403604 . ^ Sakai, Takanori; Sakaguchi, Minoru; Adachi, Yoshiko; Kawashima, Tsuneo; Awata, Norio (1992). "The Biological Fate of Sodium Prasterone Sulfate after Vaginal Administration II: Distribution after Single and Multiple Administration to Pregnant Rats".薬物動態 .7 (1):87– 101.doi :10.2133/dmpk.7.87 . ^ Somani N, Harrison S, Bergfeld WF (2008). "The clinical evaluation of hirsutism".Dermatologic Therapy .21 (5):376– 91.doi :10.1111/j.1529-8019.2008.00219.x .PMID 18844715 .S2CID 34029116 . ^ "Polycystic Ovarian Syndrome Workup" .eMedicine . 25 October 2011. Retrieved19 November 2011 .^ Vaudry, H.; Do Rego, J. L.; Burel, D.; Luu-The, V.; Pelletier, G.; Vaudry, D.; Tsutsui, K. (2011)."Neurosteroid Biosynthesis in the Brain of Amphibians" .Frontiers in Endocrinology .2 : 79.doi :10.3389/fendo.2011.00079 PMC 3355965 PMID 22649387 . ^a b c Sachdeva, Silonie (2010)."Hirsutism: Evaluation and Treatment" .Indian Journal of Dermatology . 55.1 (1):3– 7.doi :10.4103/0019-5154.60342 PMC 2856356 PMID 20418968 .
Ionotropic
GABAA Tooltip γ-Aminobutyric acid A receptor Positive modulators (abridged; seehere for a full list): α-EMTBL Alcohols (e.g.,drinking alcohol ,2M2B )Anabolic steroids Avermectins (e.g.,ivermectin )Barbiturates (e.g.,phenobarbital )Benzodiazepines (e.g.,diazepam )Bromide compounds (e.g.,potassium bromide )Carbamates (e.g.,meprobamate )Carbamazepine Chloralose Chlormezanone Clomethiazole Dihydroergolines (e.g.,ergoloid (dihydroergotoxine) )Etazepine Etifoxine Fenamates (e.g.,mefenamic acid )Flavonoids (e.g.,apigenin ,hispidulin )Fluoxetine Flupirtine Imidazoles (e.g.,etomidate )Kava constituents (e.g.,kavain )Lanthanum Loreclezole Monastrol Neuroactive steroids (e.g.,allopregnanolone ,cholesterol ,THDOC )Niacin Niacinamide Nonbenzodiazepines (e.g.,β-carbolines (e.g.,abecarnil ),cyclopyrrolones (e.g.,zopiclone ),imidazopyridines (e.g.,zolpidem ),pyrazolopyrimidines (e.g.,zaleplon ))Norfluoxetine Petrichloral Phenols (e.g.,propofol )Phenytoin Piperidinediones (e.g.,glutethimide )Propanidid Pyrazolopyridines (e.g.,etazolate )Quinazolinones (e.g.,methaqualone )Retigabine (ezogabine) ROD-188 Skullcap constituents (e.g.,baicalin )Stiripentol Sulfonylalkanes (e.g.,sulfonmethane (sulfonal) )Topiramate Valerian constituents (e.g.,valerenic acid )Volatiles /gases (e.g.,chloral hydrate ,chloroform ,diethyl ether ,paraldehyde ,sevoflurane )Negative modulators: 1,3M1B 3M2B 11-Ketoprogesterone 17-Phenylandrostenol α3IA α5IA (LS-193,268) β-CCB β-CCE β-CCM β-CCP β-EMGBL Anabolic steroids Amiloride Anisatin β-Lactams (e.g.,penicillins ,cephalosporins ,carbapenems )Basmisanil Bemegride Bicyclic phosphates (TBPS ,TBPO ,IPTBO )BIDN Bilobalide Bupropion CHEB Chlorophenylsilatrane Cicutoxin Cloflubicyne Cyclothiazide DHEA DHEA-S Dieldrin (+)-DMBB DMCM DMPC EBOB Etbicyphat FG-7142 (ZK-31906) Fiproles (e.g.,fipronil )Flavonoids (e.g.,amentoflavone ,oroxylin A )Flumazenil Fluoroquinolones (e.g.,ciprofloxacin )Flurothyl Furosemide Golexanolone Iomazenil (123 I) IPTBO Isopregnanolone (sepranolone) L-655,708 Laudanosine Lindane MaxiPost Morphine Morphine-3-glucuronide MRK-016 Naloxone Naltrexone Nicardipine Nonsteroidal antiandrogens (e.g.,apalutamide ,bicalutamide ,enzalutamide ,flutamide ,nilutamide )Oenanthotoxin Pentylenetetrazol (pentetrazol) Phenylsilatrane Picrotoxin (i.e.,picrotin ,picrotoxinin anddihydropicrotoxinin )Pregnenolone sulfate Propybicyphat PWZ-029 Radequinil Ro 15-4513 Ro 19-4603 RO4882224 RO4938581 Sarmazenil SCS Suritozole TB-21007 TBOB TBPS TCS-1105 Terbequinil TETS Thujone U-93631 Zinc ZK-93426 GABAA -ρ Tooltip γ-Aminobutyric acid A-rho receptor
Metabotropic
GABAB Tooltip γ-Aminobutyric acid B receptor
GR Tooltip Glucocorticoid receptor
Receptor (ligands )
GlyR Tooltip Glycine receptor Positive modulators: Alcohols (e.g.,brometone ,chlorobutanol (chloretone) ,ethanol (alcohol) ,tert -butanol (2M2P)tribromoethanol ,trichloroethanol ,trifluoroethanol )Alkylbenzene sulfonate Anandamide Barbiturates (e.g.,pentobarbital ,sodium thiopental )Chlormethiazole D12-116 Dihydropyridines (e.g.,nicardipine )Etomidate Ginseng constituents (e.g.,ginsenosides (e.g.,ginsenoside-Rf ))Glutamic acid (glutamate) Ivermectin Ketamine Neuroactive steroids (e.g.,alfaxolone ,pregnenolone (eltanolone) ,pregnenolone acetate ,minaxolone ,ORG-20599 )Nitrous oxide Penicillin G Propofol Tamoxifen Tetrahydrocannabinol Triclofos Tropeines (e.g.,atropine ,bemesetron ,cocaine ,LY-278584 ,tropisetron ,zatosetron )Volatiles /gases (e.g.,chloral hydrate ,chloroform ,desflurane ,diethyl ether (ether) ,enflurane ,halothane ,isoflurane ,methoxyflurane ,sevoflurane ,toluene ,trichloroethane (methyl chloroform) ,trichloroethylene )Xenon Zinc Antagonists: 2-Aminostrychnine 2-Nitrostrychnine 4-Phenyl-4-formyl-N-methylpiperidine αEMBTL Bicuculline Brucine Cacotheline Caffeine Colchicine Colubrine Cyanotriphenylborate Dendrobine Diaboline Endocannabinoids (e.g.,2-AG ,anandamide (AEA) )Gaboxadol (THIP) Gelsemine iso-THAZ Isobutyric acid Isonipecotic acid Isostrychnine Laudanosine N-Methylbicuculline N-Methylstrychnine N,N-Dimethylmuscimol Nipecotic acid Pitrazepin Pseudostrychnine Quinolines (e.g.,4-hydroxyquinoline ,4-hydroxyquinoline-3-carboxylic acid ,5,7-CIQA ,7-CIQ ,7-TFQ ,7-TFQA )RU-5135 Sinomenine Strychnine Thiocolchicoside Tutin Negative modulators: Amiloride Benzodiazepines (e.g.,bromazepam ,clonazepam ,diazepam ,flunitrazepam ,flurazepam )Corymine Cyanotriphenylborate Daidzein Dihydropyridines (e.g.,nicardipine ,nifedipine ,nitrendipine )Furosemide Genistein Ginkgo constituents (e.g.,bilobalide ,ginkgolides (e.g.,ginkgolide A ,ginkgolide B ,ginkgolide C ,ginkgolide J ,ginkgolide M ))Imipramine NBQX Neuroactive steroids (e.g.,3α-androsterone sulfate ,3β-androsterone sulfate ,deoxycorticosterone ,DHEA sulfate ,pregnenolone sulfate ,progesterone )Opioids (e.g.,codeine ,dextromethorphan ,dextrorphan ,levomethadone ,levorphanol ,morphine ,oripavine ,pethidine ,thebaine )Picrotoxin (i.e.,picrotin andpicrotoxinin )PMBA Riluzole Tropeines (e.g.,bemesetron ,LY-278584 ,tropisetron ,zatosetron )Verapamil Zinc NMDAR Tooltip N-Methyl-D-aspartate receptor
Transporter (blockers )
GlyT1 Tooltip Glycine transporter 1 GlyT2 Tooltip Glycine transporter 2
Angiopoietin CNTF EGF (ErbB)
FGF
FGFR1 FGFR2 Agonists: Ersofermin FGF (1 ,2 (bFGF) ,3 ,4 ,5 ,6 ,7 (KGF ),8 ,9 ,10 (KGF2) ,17 ,18 ,22 )Palifermin Repifermin Selpercatinib Sprifermin Trafermin FGFR3 FGFR4 Unsorted
HGF (c-Met) IGF
LNGF (p75NTR ) PDGF RET (GFL)
SCF (c-Kit) TGFβ Trk
TrkA Negative allosteric modulators: VM-902A TrkB Agonists: 3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF BNN-20 Deoxygedunin Deprenyl Diosmetin DMAQ-B1 HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 R13 TDP6 TrkC
VEGF Others Additional growth factors: Adrenomedullin Colony-stimulating factors (seehere instead)Connective tissue growth factor (CTGF) Ephrins (A1 ,A2 ,A3 ,A4 ,A5 ,B1 ,B2 ,B3 )Erythropoietin (seehere instead)Glucose-6-phosphate isomerase (GPI; PGI, PHI, AMF) Glia maturation factor (GMF) Hepatoma-derived growth factor (HDGF) Interleukins /T-cell growth factors (seehere instead)Leukemia inhibitory factor (LIF) Macrophage-stimulating protein (MSP; HLP, HGFLP) Midkine (NEGF2) Migration-stimulating factor (MSF; PRG4) Oncomodulin Pituitary adenylate cyclase-activating peptide (PACAP) Pleiotrophin Renalase Thrombopoietin (seehere instead)Wnt signaling proteins Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture)
AMPAR Tooltip α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor KAR Tooltip Kainate receptor NMDAR Tooltip N-Methyl-D-aspartate receptor
TRPA
Activators 4-Hydroxynonenal 4-Oxo-2-nonenal 5,6-EET 12S-HpETE 15-Deoxy-Δ12,14 -prostaglandin J2 α-Sanshool (ginger ,Sichuan andmelegueta 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 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 andmelegueta 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 andmelegueta 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 LowpH (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 andmelegueta peppers )Tetrahydrocannabivarin (cannabis )Thymol (thyme ,oregano )Tinyatoxin (Euphorbia resinifera /pooissonii Tramadol Vanillin (vanilla )Zucapsaicin Blockers
CAR Tooltip Constitutive androstane receptor PXR Tooltip Pregnane X receptor
