Table 2.

Structures, receptor affinities, and actions of anti-emetic drugs.

	D1	D2	D3	D4	α1	α2	H1	M	5-HT2A	5-HT3A	Other
Muscarinic Receptor Antagonist
Scopolamine		Ki >10,000 nM (rat)13					Ki >10,000 nM (rat)13	M1 9.0 M2 8.7 M3 9.4 M4 9.5 antagonist
Histamine H1 Receptor Antagonists
Diphenhydramine		Ki >10,000 nM (rat)13					7.9 antagonist	pA2 7.1 antagonist (rat)7
Promethazine		Ki 240 nM (rat)13					9.6 antagonist	Ki 21 nM (rat)13
Cyclizine							8.4 antagonist				Pre-ganglionic cholinergic inhibition (animals)15
Cinnarizine							antagonist16	antagonist16			Blocks L-type and T-type calcium channels16
Phenothiazines
Prochlorperazine	7.1 antagonist	8.4 antagonist	8.4 antagonist	6.1 antagonist	Ki 200 nM (rat)14		p1C50 6.7 inverse agonist6 8.28	Ki 2,100 nM (rat)13	8.23	Inactive (rat)10
Chlorpromazine	7.1 antagonist	7.0–7.6 antagonist	7.2–7.5 antagonist	7.8 antagonist	α1A Ki 0.28 nM12	α2A 5.9–6.6 α2B 7.2–8.3 α2C 6.9–7.4 antagonist at each	8.2 antagonist	Ki 47 M3 (rat)12	8.1 inverse agonist	Inactive (rat)10	D5 6.9 antagonist 5-HT1A 6.2 antagonist 5-HT2C 7.6–8.2 antagonist 5-HT6 7.7–7.8 inverse agonist 5-HT7 7.6 inverse agonist
Fluphenazine	7.7 antagonist	8.8 antagonist			Ki 8.1 nM (rat)14		7.7 antagonist	Ki 340nM (rat)13	7.5 antagonist	Inactive (rat)10	D5 7.9 antagonist 5-HT7 7.9 inverse agonist 5-HT6 7.3–7.4 inverse agonist
Levomepromazine	Ki 54.31	Ki8.61	Ki8.31				Kd 0.58nM antagonist2
Mirtazapine					α2A 7.7 antagonist	α2C 7.7 antagonist	p1C50 9.6 inverse agonist68.98		7.2 antagonist		5-HT2C 7.4 antagonist
Metoclopramide
Metoclopramide		7.5 antagonist (mouse)			Ki >10,000 nM (rat)		Ki 1,100 nM (rat)13	Ki >10,000 nM (rat)13		5-HT3A 6.0–6.4 antagonist 5-HT3AB 5.7 antagonist	5-HT4 6 agonist (mouse)
Butyrophenones
Haloperidol	7.6–8.2 antagonist	7.4–8.8 antagonist	7.5–8.6 antagonist	8.7–8.8 antagonist	Ki 46 nM5	Ki 360 nM5	5.7–6.1 antagonist	Ki >1,000 nM at M1, M2, M3 (rat)5	6.7–7.3 antagonist	Ki >1,000 nM5	5-HT1D 6.6 antagonist 5-HT7 6.3–6.6 antagonist 5-HT2B 5.8–6.4 antagonist 5-HT1A 5.7–5.8 antagonist
Droperidol		Ki 3 nM (rat)11			Ki 1.4 nM (rat)11		Ki 2,500 nM (rat)11		Ki 4.6 nM (rat)11	Inactive (rat)10
Domperidone		7.9–8.4 antagonist	7.1–7.6 antagonist	Ki 30.4 nM4	Ki α1A, 71; α1B, 530; α1D, 710 nM9					Inactive (rat)10
Second generation anti-psychotics
Olanzapine	Ki 31 nM (rat)5	8.7 antagonist		Ki 27 nM (rat)5	α1A Ki 115 nM12	α2A Ki 314; α2B 81.6; α2C 28.8 nM12	8.7–9.2 antagonist	Ki 105 nM at ${\text{M}}_3^{12}$	8.6–8.9 antagonist	Ki 57 nM (rat)5	5-HT2C 8.1–8.4 inverse agonist 5-HT6 8 inverse agonist 5-HT7 6.5 antagonist
5-HT3 Receptor Antagonists
Granisetron		Inactive (>10,000 nM) (rat)10								5-HT3A ~8.6–8.8 antagonist
Ondansetron										5-HT3A ~7.8–8.3 5-HT3AB 7.8 antagonist
Tropisetron		Inactive (>10,000 nM) (rat)10								5-HT3A 8.5–8.8 antagonist	5-HT4 6.3–7.1 antagonist
Palonsetron										5-HT3A 10.5 antagonist
NK1 receptor antagonists
Aprepitant											NK1 10.1 antagonist

Data are from http://www.guidetopharmacology.org/ and are given as pK_i-values for the human receptors (usually recombinant); primary affinities are in bold. Additional information on drug affinity for human receptors (unless otherwise specified) is provided in italics together with references, listed below. Little information is known for cyclizine or for cinnarizine, particularly in terms of their interactions with human receptors and mechanisms. Clarke and Dundee (1971) describe significant sedation/drowsiness associated with promethazine, thiethylperazine, cyclizine and hyoscine. ¹Srivastava et al., 2009; ²Kanba and Richelson, 1984; ³Meltzer et al., 1989; ⁴Moreland et al., 2004; ⁵Bymaster et al., 1996; ⁶Bakker et al., 2007; ⁷Liu et al., 2006; ⁸Appl et al., 2012; ⁹Keiser et al., 2009; ¹⁰Hamik and Peroutka, 1989; ¹¹Peroutka and Synder, 1980; ¹²Kroeze et al., 2003; ¹³Peroutka and Snyder, 1982; ¹⁴Ison and Peroutka, 1986; ¹⁵Norton et al., 1954; ¹⁶https://www.drugbank.ca/drugs/DB00568#BE0000442.