TABLE 1

Compounds modulating 5-HT₃Rs

Drug or Compound	Species	Receptor Subtype	K_i, IC₅₀, or EC₅₀	Main Effect, Application, or Therapeutic Use	Reference
Agonist
5-HT	—	5-HT_3A	1.56–3.4 µM	Neurotransmitter	Thompson and Lummis, 2003
	N1E-115^{^a}	—	1.8 µM		Hussy et al., 1994
	SCG (mouse)	—	2.6 µM		Hussy et al., 1994
	NG108-15^{^b}	5-HT_3A	3.5 µM		Hussy et al., 1994
	Human^{^c}	5-HT_3A	123 nM		Hope et al., 1996
	Rat	—	219 nM		Steward et al., 1995
2-Methyl-5-HT	N1E-115^{^a}	—	11 µM	Derivative of serotonin	Hussy et al., 1994
	SCG (mouse)	—	11.8 µM		Hussy et al., 1994
	NG108-15^{^b}	5-HT_3A	13 µM		Hussy et al., 1994
	Human^{^c}	5-HT_3A	224 nM		Hope et al., 1996
	Human^{^c}	5-HT_3A	4.1 µM		Davies et al., 1999
	Rat	—	562 nM		Steward et al., 1995
m-CPBG	Mouse^{^d}	5-HT_3A	400 nM	Pharmacological tool	Downie et al., 1994
	Human^{^c}	5-HT_3A	19.5 nM		Hope et al., 1996
	Human^{^c}	5-HT_3A	480 nM		Dubin et al., 1999
	Rat	—	1.5 nM		Kilpatrick et al., 1990
	Rat	—	4.77 nM		Steward et al., 1995
Phenylbiguanide	Mouse^{^d}	5-HT_3A	18 µM	Pharmacological tool	Downie et al., 1994
	NG 108-15^{^b}	—	1.2 µM		Dukat et al., 1996
	NG 108-15^{^b}	—	1.8 µM		Downie et al., 1995
	Human^{^c}	5-HT_3A	2.4 µM		Hope et al., 1996
	Human^{^c}	5-HT_3A	10.1 µM		Dubin et al., 1999
	Rat	—	135 nM		Steward et al., 1995
Varenicline	Human^{^d}	5-HT_3A	5.9 μM	Used for smoking cessation	Lummis et al., 2011
	Human^{^c}	5-HT_3A	0.27 μM
	Mouse^{^d}	5-HT_3A	18.3 μM
	Human^{^c}	5-HT_3A	4.9 μM
m-CPP	Mouse	5-HT_3A	400 nM	Nonselective agonist with psychoactive properties	Downie et al., 1994
	Human^{^d}	5-HT_3A	480 nM		Dubin et al., 1999
	Human^{^d}	5-HT_3A	19.5 nM		Hope et al., 1996
	Rat	—	4.77 nM		Steward et al., 1995
Quipazine	Human^{^d}	5-HT_3A	27 nM	Piperazine analog with antidepressant and oxytocic properties	Dubin et al., 1999
Dopamine	Human^{^d}	5-HT_3A	135 μM	Neurotransmitter	Dubin et al., 1999
2-Chloro-phenylbiguanide	NG 108-15^{^b}	—	62 nM	—	Dukat et al., 1996
3-Chloro-phenylbiguanide	NG 108-15^{^b}	—	17 nM	—	Dukat et al., 1996
4-Chloro-phenylbiguanide	NG 108-15^{^b}	—	200 nM	—	Dukat et al., 1996
2-Naphthylbiguanide	NG 108-15^{^b}	—	12 nM	—	Dukat et al., 1996
2-Methoxy-5-chloro-phenylpiperazine-	NG 108-15^{^b}	—	40 nM	—	Dukat et al., 1996
3,4-Dichlorophenylguanidine	NG 108-15^{^b}	—	3.1 nM	—	Glennon et al., 2003
3,4,5-Trichlorophenylbiguanide	NG 108-15^{^b}	—	0.7 nM	—	Glennon et al., 2003
3,4-Dichlorophenylbiguanide	NG 108-15^{^b}	—	3.1 nM	—	Glennon et al., 2003
N-Methylquipazine dimaleate	Rat	—	4.7 nM	—	Glennon et al., 1989
RS 56812 hydrochloride	Rat	—	—	—	Clark et al., 1995
SR 57227A	Rat	—	2.8 nM	Pharmacological tool	Bachy et al., 1993
	NG 108-15^{^b}	—	250 nM		Bachy et al., 1993
Competitive antagonists
Granisetron	Mouse^{^d}	5-HT_3A	0.14 nM	Antiemetic used for CINV	Downie et al., 1994
	Human^{^c}	5-HT_3A	1.44 nM		Hope et al., 1996
	N1E-115^{^a}	—	0.23 nM		Lummis et al., 1993
	Rat	—	5.13 nM		Steward et al., 1995
Tropisetron	NG 108-15^{^b}	—	3.85 nM	Antiemetic used for CINV	Downie et al., 1995
	Rat	—	4.9 nM		Steward et al., 1995
	Rabbit	—	0.046 nM		Peters et al., 1993
Ondansetron	Mouse^{^d}	5-HT_3A	0.44 nM	Antiemetic used for CINV	Gill et al., 1995
	Human^{^c}	5-HT_3A	4.9 nM		Hope et al., 1996
	N1E-115^{^a}	—	7.4 nM		Lummis et al., 1990
	Mouse (NCB-20 cells)	—	0.25 nM		Lambert et al., 1989
	Rat	—	46.8 nM		Steward et al., 1995
	Rabbit	—	0.057 nM		Peters et al., 1993
Dolasetron	NG 108-15^{^b}	—	20.03 nM	Antiemetic	Boeijinga et al., 1992
Azasetron	Rat	—	2.9 nM	Antiemetic	Sato et al., 1992
Ramosetron	Human^{^c}	—	0.091 nM	Antiemetic, also used for IBS	Hirata et al., 2007
	Rat	—	0.22 nM		Hirata et al., 2007
Alosetron	Guinea pig	—	50 nM	Used for IBS-D	Zhai et al., 1999
	Human^{^c}	—	0.29 nM		Hirata et al., 2007
	Rat	—	0.71 nM		Hirata et al., 2007
Cilansetron	Human^{^c}	—	0.56 nM	Used for IBS-D	Hirata et al., 2007
	Rat	—	0.64 nM		Hirata et al., 2007
Palonosetron (RS 25259-197)	Guinea pig	—	5.01 nM	Antiemetic used for delayed CINV	Thompson and Lummis, 2007
Indisetron	Rat	—	1.82 nM	Antiemetic	Taniguchi, 2004
Bemesetron (MDL-72222)	N1E-115^{^a}	—	16 nM	Antiemetic	Lummis et al., 1990
	N1E-115^{^a}	—	3.5 nM		Hussy et al., 1994
	SCG (mouse)	—	5 nM		Hussy et al., 1994
	NG108-15^{^b}	5-HT_3A	3.5 nM		Hussy et al., 1994
	Rat	—	30.2 nM		Steward et al., 1995
	Rabbit	—	0.33 nM		Peters et al., 1993
Mirtazapine	Human^{^c}	5-HT_3A	2.9 nM	Atypical antidepressant	Eisensamer et al., 2003
Zacopride	Human	—	0.38 nM	Antiemetic, gastroprokinetic, and anxiolytic	Nagakura et al., 1999
(S)-Zacopride	Rat	—	0.95 nM		Steward et al., 1995
(R)-Zacopride	Rat	—	10.9 nM		Steward et al., 1995
Renzapride	Rat	—	67.6 nM	Antiemetic	Steward et al., 1995
Clozapine	Rat	—	269 nM	Atypical antipsychotic	Steward et al., 1995
Chloroquine	Human^{^d}	5-HT_3A	24.3 μM	Antimalarial agent	Thompson and Lummis, 2008
Mefloquine	Human^{^d}	5-HT_3A	0.66 μM		Thompson and Lummis, 2008
Quinine	Human^{^d}	5-HT_3A	1.06 μM		Thompson and Lummis, 2008
Diltiazem	N1E-115^{^a}	5-HT_3A	5.5 nM	L-type calcium channel blocker, used for hypertension, angina, and some heart arrhythmias	Gunthorpe and Lummis, 1999
	Human^{^d}	5-HT_3A	21 µM		Thompson et al., 2011a
(+)-Verapamil	N1E-115^{^a}	5-HT_3A	2.6 nM		Hargreaves et al., 1996
(−)-Verapamil	N1E-115^{^a}	5-HT_3A	13.1 nM		Hargreaves et al., 1996
Cannabidiol	Human^{^d}	5-HT_3A	0.6 nM	Nonpsychotropic cannabinoid	Yang et al., 2010
Poria cocos triterpenoids	Human^{^d}	5-HT_3A	3 nM	Medicinal plant used for chronic gastritis, edema, nephritis, nausea, and emesis	Lee et al., 2009
Boldine	Human^{^c}	5-HT_3A	5.5 µM	Aporphine alkaloid from Peumus boldus leaves with antioxidant properties	Walstab et al., 2014
	Human^{^c}	5-HT_3AB	35.5 µM		Walstab et al., 2014
Morphine	Human^{^c}	5-HT_3A	13 µM	Opioid analgesic	Baptista-Hon et al., 2012
	Human^{^c}	5-HT_3AB	8 µM		Baptista-Hon et al., 2012
Scopolamine	Human^{^c}	5-HT_3A	2.09 μM	Muscarinic antagonist used for postoperative nausea and vomiting and motion sickness	Lochner and Thompson, 2016
Atropine	Human^{^c}	5-HT_3A	1.74 μM	Muscarinic antagonist used as cycloplegic and mydriatic, also for bradycardia	Lochner and Thompson, 2016
Quercetin	Human^{^d}	5-HT_3A	64.7 μM	Flavonoid with analgesic, prokinetic, anticonvulsant, sedative, and anxiolytic properties	Lee et al., 2005a
Noncompetitive antagonists
Alisol extract	Human^{^d}	5-HT_3A	1.7–35 μM	Traditional medicine with diuretic, hypolipemic, antiatherosclerotic, and antihepatitis B virus properties	Lee et al., 2010
Anandamide	Human^{^c}	5-HT_3A	129.6 nM	Endocannabinoid	Barann et al., 2002
Δ9-THC	Human^{^c}	5-HT_3A	38.4 nM	Main psychoactive component of cannabis	Barann et al., 2002
WIN55,212-2	Human^{^c}	5-HT_3A	103.5 nM	Synthetic, nonselective cannabinoid	Barann et al., 2002
Bilobalide	Human^{^d}	5-HT_3A	468 μM	Noncompetitive antagonist of GABA and glycine receptors	Thompson et al., 2011a
	Human^{^d}	5-HT_3AB	3100 μM		Thompson et al., 2011a
Ginkgolide B	Human^{^d}	5-HT_3A	727 μM		Thompson et al., 2011a
	Human^{^d}	5-HT_3AB	3900 μM		Thompson et al., 2011a
Picrotoxinin	Human^{^d}	5-HT_3A	11 μM		Thompson et al., 2011a
	Human^{^d}	5-HT_3AB	62 μM		Thompson et al., 2011a
Picrotoxin	Mouse^{^c}	5-HT_3A	41.2 μM	GABA_A receptor antagonist	Das and Dillon, 2005
Citral	Human^{^d}	5-HT_3A	120 µM	Terpenoid used as flavoring agent	Jarvis et al., 2016
Linalool	Human^{^d}	5-HT_3A	141 µM		Jarvis et al., 2016
Eucalyptol	Human^{^d}	5-HT_3A	258 µM		Jarvis et al., 2016
(−)-Menthol	Human^{^c}	5-HT_3A	179.41 µM	Monoterpene from mentha used as flavoring agent	Walstab et al., 2014
Ginger extract	Human^{^c}	5-HT_3A	74.9 nM	Traditional medicine used for spa	Walstab et al., 2013
	Human^{^c}	5-HT_3AB	77.2 nM		Walstab 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.