Compounds modulating 5-HT3Rs

Drug or CompoundSpeciesReceptor SubtypeKi, IC50, or EC50Main Effect, Application, or Therapeutic UseReference
 5-HT5-HT3A1.56–3.4 µMNeurotransmitterThompson and Lummis, 2003
N1E-115a1.8 µMHussy et al., 1994
SCG (mouse)2.6 µMHussy et al., 1994
NG108-15b 5-HT3A3.5 µMHussy et al., 1994
Humanc5-HT3A123 nMHope et al., 1996
Rat219 nMSteward et al., 1995
 2-Methyl-5-HTN1E-115a11 µMDerivative of serotoninHussy et al., 1994
SCG (mouse)11.8 µMHussy et al., 1994
NG108-15b5-HT3A13 µMHussy et al., 1994
Humanc5-HT3A224 nMHope et al., 1996
Humanc5-HT3A4.1 µMDavies et al., 1999
Rat562 nMSteward et al., 1995
m-CPBGMoused 5-HT3A400 nMPharmacological toolDownie et al., 1994
Humanc 5-HT3A19.5 nMHope et al., 1996
Humanc 5-HT3A480 nMDubin et al., 1999
Rat1.5 nMKilpatrick et al., 1990
Rat4.77 nMSteward et al., 1995
 PhenylbiguanideMoused5-HT3A18 µMPharmacological toolDownie et al., 1994
NG 108-15b1.2 µMDukat et al., 1996
NG 108-15b1.8 µMDownie et al., 1995
Humanc5-HT3A2.4 µMHope et al., 1996
Humanc 5-HT3A10.1 µMDubin et al., 1999
Rat135 nMSteward et al., 1995
 VareniclineHumand 5-HT3A5.9 μMUsed for smoking cessationLummis et al., 2011
Humanc 5-HT3A0.27 μM
Moused 5-HT3A18.3 μM
Humanc 5-HT3A4.9 μM
m-CPPMouse5-HT3A400 nMNonselective agonist with psychoactive propertiesDownie et al., 1994
Humand 5-HT3A480 nMDubin et al., 1999
Humand 5-HT3A19.5 nMHope et al., 1996
Rat4.77 nMSteward et al., 1995
 QuipazineHumand 5-HT3A27 nMPiperazine analog with antidepressant and oxytocic propertiesDubin et al., 1999
 DopamineHumand 5-HT3A135 μMNeurotransmitterDubin et al., 1999
 2-Chloro-phenylbiguanideNG 108-15b62 nMDukat et al., 1996
 3-Chloro-phenylbiguanideNG 108-15b17 nMDukat et al., 1996
 4-Chloro-phenylbiguanideNG 108-15b200 nMDukat et al., 1996
 2-NaphthylbiguanideNG 108-15b12 nMDukat et al., 1996
 2-Methoxy-5-chloro-phenylpiperazine-NG 108-15b40 nMDukat et al., 1996
 3,4-DichlorophenylguanidineNG 108-15b3.1 nMGlennon et al., 2003
 3,4,5-TrichlorophenylbiguanideNG 108-15b0.7 nMGlennon et al., 2003
 3,4-DichlorophenylbiguanideNG 108-15b3.1 nMGlennon et al., 2003
 N-Methylquipazine dimaleateRat4.7 nMGlennon et al., 1989
 RS 56812 hydrochlorideRatClark et al., 1995
 SR 57227ARat2.8 nMPharmacological toolBachy et al., 1993
NG 108-15b250 nMBachy et al., 1993
Competitive antagonists
 GranisetronMoused 5-HT3A0.14 nMAntiemetic used for CINVDownie et al., 1994
Humanc5-HT3A1.44 nMHope et al., 1996
N1E-115a0.23 nMLummis et al., 1993
Rat5.13 nMSteward et al., 1995
 TropisetronNG 108-15b3.85 nMAntiemetic used for CINVDownie et al., 1995
Rat4.9 nMSteward et al., 1995
Rabbit0.046 nMPeters et al., 1993
 OndansetronMoused 5-HT3A0.44 nMAntiemetic used for CINVGill et al., 1995
Humanc5-HT3A4.9 nMHope et al., 1996
N1E-115a7.4 nMLummis et al., 1990
Mouse (NCB-20 cells)0.25 nMLambert et al., 1989
Rat46.8 nMSteward et al., 1995
Rabbit0.057 nMPeters et al., 1993
 DolasetronNG 108-15b20.03 nMAntiemeticBoeijinga et al., 1992
 AzasetronRat2.9 nMAntiemeticSato et al., 1992
 RamosetronHumanc0.091 nMAntiemetic, also used for IBSHirata et al., 2007
Rat0.22 nMHirata et al., 2007
 AlosetronGuinea pig50 nMUsed for IBS-DZhai et al., 1999
Humanc0.29 nMHirata et al., 2007
Rat0.71 nMHirata et al., 2007
 CilansetronHumanc0.56 nMUsed for IBS-DHirata et al., 2007
Rat0.64 nMHirata et al., 2007
 Palonosetron (RS 25259-197)Guinea pig5.01 nMAntiemetic used for delayed CINVThompson and Lummis, 2007
 IndisetronRat1.82 nMAntiemeticTaniguchi, 2004
 Bemesetron (MDL-72222)N1E-115a16 nMAntiemeticLummis et al., 1990
N1E-115a3.5 nMHussy et al., 1994
SCG (mouse)5 nMHussy et al., 1994
NG108-15b 5-HT3A3.5 nMHussy et al., 1994
Rat30.2 nMSteward et al., 1995
Rabbit0.33 nMPeters et al., 1993
 MirtazapineHumanc 5-HT3A2.9 nMAtypical antidepressantEisensamer et al., 2003
 ZacoprideHuman0.38 nMAntiemetic, gastroprokinetic, and anxiolyticNagakura et al., 1999
 (S)-ZacoprideRat0.95 nMSteward et al., 1995
 (R)-ZacoprideRat10.9 nMSteward et al., 1995
 RenzaprideRat67.6 nMAntiemeticSteward et al., 1995
 ClozapineRat269 nMAtypical antipsychoticSteward et al., 1995
 ChloroquineHumand 5-HT3A24.3 μMAntimalarial agentThompson and Lummis, 2008
 MefloquineHumand5-HT3A0.66 μMThompson and Lummis, 2008
 QuinineHumand5-HT3A1.06 μMThompson and Lummis, 2008
 DiltiazemN1E-115a5-HT3A5.5 nML-type calcium channel blocker, used for hypertension, angina, and some heart arrhythmiasGunthorpe and Lummis, 1999
Humand5-HT3A21 µMThompson et al., 2011a
 (+)-VerapamilN1E-115a 5-HT3A2.6 nMHargreaves et al., 1996
 (−)-VerapamilN1E-115a5-HT3A13.1 nMHargreaves et al., 1996
 CannabidiolHumand5-HT3A0.6 nMNonpsychotropic cannabinoidYang et al., 2010
 Poria cocos triterpenoidsHumand 5-HT3A3 nMMedicinal plant used for chronic gastritis, edema, nephritis, nausea, and emesisLee et al., 2009
 BoldineHumanc5-HT3A5.5 µMAporphine alkaloid from Peumus boldus leaves with antioxidant propertiesWalstab et al., 2014
Humanc5-HT3AB35.5 µMWalstab et al., 2014
 MorphineHumanc5-HT3A13 µMOpioid analgesicBaptista-Hon et al., 2012
Humanc5-HT3AB8 µMBaptista-Hon et al., 2012
 ScopolamineHumanc5-HT3A2.09 μMMuscarinic antagonist used for postoperative nausea and vomiting and motion sicknessLochner and Thompson, 2016
 AtropineHumanc5-HT3A1.74 μMMuscarinic antagonist used as cycloplegic and mydriatic, also for bradycardiaLochner and Thompson, 2016
 QuercetinHumand5-HT3A64.7 μMFlavonoid with analgesic, prokinetic, anticonvulsant, sedative, and anxiolytic propertiesLee et al., 2005a
Noncompetitive antagonists
 Alisol extractHumand5-HT3A1.7–35 μMTraditional medicine with diuretic, hypolipemic, antiatherosclerotic, and antihepatitis B virus propertiesLee et al., 2010
 AnandamideHumanc5-HT3A129.6 nMEndocannabinoidBarann et al., 2002
 Δ9-THCHumanc 5-HT3A38.4 nMMain psychoactive component of cannabisBarann et al., 2002
 WIN55,212-2Humanc 5-HT3A103.5 nMSynthetic, nonselective cannabinoidBarann et al., 2002
 BilobalideHumand 5-HT3A468 μMNoncompetitive antagonist of GABA and glycine receptorsThompson et al., 2011a
Humand 5-HT3AB3100 μMThompson et al., 2011a
 Ginkgolide BHumand 5-HT3A727 μMThompson et al., 2011a
Humand5-HT3AB3900 μMThompson et al., 2011a
 PicrotoxininHumand5-HT3A11 μMThompson et al., 2011a
Humand5-HT3AB62 μMThompson et al., 2011a
 PicrotoxinMousec5-HT3A41.2 μMGABAA receptor antagonistDas and Dillon, 2005
 CitralHumand5-HT3A120 µMTerpenoid used as flavoring agentJarvis et al., 2016
 LinaloolHumand5-HT3A141 µMJarvis et al., 2016
 EucalyptolHumand5-HT3A258 µMJarvis et al., 2016
 (−)-MentholHumanc5-HT3A179.41 µMMonoterpene from mentha used as flavoring agentWalstab et al., 2014
 Ginger extractHumanc5-HT3A74.9 nMTraditional medicine used for spaWalstab et al., 2013
Humanc5-HT3AB77.2 nMWalstab et al., 2013
  • Dashes indicate not identified or not applicable. CINV, chemotherapy-induced nausea and vomiting; IBS-D, diarrhea dominant IBS; m-CPP, meta-chlorophenylpiperazine; SCG, superior cervical ganglion.

  • a Mouse neuroblastoma cells.

  • b Mouse neuroblastoma × rat glioma hybrid cells.

  • c Expressed in human embryonic kidney 293 cells.

  • d Expressed in Xenopus laevis oocytes.