TABLE 7

Functional activity (EC₅₀) and binding potency (K_i) of endogenous, selected psychoactive, nonselective, and selective TAAR1 agonists in rats, mice, and humans

Values for EC₅₀ and K_i are given in micromolar, whereas values for efficacy are given in percentages and indicate maximal cAMP levels reached compared with 10 μM 2-phenylethylamine.

TAAR1 Agonist	Rat TAAR1			Mouse TAAR1			Human TAAR1
TAAR1 Agonist	EC₅₀	Efficacy	K_i	EC₅₀	Efficacy	K_i	EC₅₀	Efficacy	K_i
Endogenous ligands
PEA^{^a}	0.11	100	0.24	0.20	102	0.31	0.26	104
TYR^{^a}	0.030	94	0.059	0.28	88	0.38	0.99	91
TRP^{^a}	0.41	91	0.13	2.7	117	1.4	21	73
Octopamine^{^b}	2.1	100		20	100		10	100
Dopamine^{^b}	5.1	50		12	50		16	50
Serotonin^{^b}	5.2	50		>50			>50	100
3-MT^{^c}							0.70
Amphetamine like^{^a}
Amphetamine	0.66	91	0.23	0.53	90	0.089	2.8	91
4-fluoroamphetamine	0.069	78	0.081	0.13	77	0.32	3.5	67
4-methylamphetamine	0.11	93	0.10	0.071	94	0.15	>30
Methamphetamine	0.85	73	0.35	0.73	78	0.55	5.3	70
4-fluoromethamphetamine	0.16	76	0.24	0.46	69	1.7	6.2	44
MDMA	1.0	56	0.37	4.0	71	2.4	35	26
MDA	0.74	86	0.25	0.58	102	0.16	3.6	11
Cathinone	1.2	28	2.2	1.2	66	2.1	6.9	53
Methcathinone	8.2	41	4.1	6.8	64	>10	>30
Benzofurans^{^a}
4-(2-aminopropyl)benzofuran (4-APB)	0.16	75	0.11	0.85	72	2.1	4.1	50
5-(2-aminopropyl)benzofuran (5-APB)	0.067	88	0.042	0.13	67	0.11	6.1	43
6-(2-aminopropyl)benzofuran (6-APB)	0.042	90	0.052	0.067	93	0.056	7.2	47
7-(2-aminopropyl)benzofuran (7-APB)	0.058	109	0.066	0.11	95	0.13	0.63	89
6-aminopropyl-2,3-dihydrobenzofuran (6-APDB)	1.0	83	1.0	0.51	95	0.21	>10
Phenethylamines^{^a}
2,5-dimethoxy-4-bromo-phenethylamine (2C-B)	0.24	57	0.079	2.3	69	2.2	3.3	10
8-bromo-2,3,6,7-benzodihydro-difuran-ethylamine (2C-B-Fly)	0.27	48	0.029	1.8	49	0.71	>30
4-ethyl-2,5-dimethoxyphenethylamine (2C-E)	0.18	72	0.066	1.1	64	1.2	>10
2,5-dimethoxyphenethylamine (2C-H)	1.5	80	0.90	7.5	56	11	6.5	53
2,5-dimethoxy-4-propyl-phenethylamine (2C-P)	0.030	84	0.020	0.56	91	0.28	4.2	72
Mescaline	3.7	37	3.3	4.8	25	11	>10
(−)-Ephedrine	2.5	42	3.7	14	31	>15	>10
4-thio-substituted phenethylamines^{^d}
2C-T-3			0.0080			0.47	>30
2C-T-7 (“blue mystic”)			0.010			0.31	>30
2C-T-19			0.0048			0.096	>30
2C-T-31			0.0052			0.055	>30
TRPs^{^a}
Psilocin	0.92	85	1.4	2.7	80	17	>30
DMT	1.5	81	2.2	1.2	73	3.3	>10
Ergolines
Lysergic acid diethylamide (LSD)^{^a}	1.4	29	0.45	9.7	13	10	>20
Piperazines^{^a}
m-Chlorophenylpiperazine (m-CPP)	0.15	60	0.054	3.2	40	6.6	>30
Trifluoromethylphenylpiperazine (TFMPP)	0.75	59	0.38	3.8	44	2.3	>30
Aminoindanes^{^a}
2-aminoindane (2-AI)	0.11	90	0.31	0.33	54	2.1	1.5	110
N-methyl-2-AI	0.37	63	0.53	0.94	108	2.6	3.3	54
5-iodo-2-aminoindane (5-IAI)	0.033	96	0.030	0.41	36	1.1	3.2	33
5,6-methylenedioxy-2-aminoindane (MDAI)	0.22	95	0.57	0.52	99	1.8	4.1	30
Miscellaneous nonselective compounds
Apomorphine^{^e}	0.99	79	0.37	2.5	59	0.37	>20		0.70
Ractopamine^{^f}				0.016	100
3IT^{^g}^,^{^h}	0.014			0.090	61		1.7	56
Clonidine^ⁱ				0.21			0.97
Guanabenz^ⁱ				0.007			0.025
Idazoxan^ⁱ				0.11			6.7
Selective compounds
RO5073012^{^j}	0.025	24	0.0011	0.023	26	0.0032	0.025	34	0.0058
RO5166017^{^k}	0.014	90	0.0027	0.0033	65	0.0019	0.055	95	0.031
RO5203648^{^l}	0.0068	59	0.0010	0.0040	48	0.0005	0.030	73	0.0068
RO5256390^{^m}	0.0051	107	0.0029	0.0020	79	0.0044	0.016	98	0.024
RO5263397^{^m}	0.047	76	0.0091	0.0013	59	0.0009	0.017	81	0.0041
Selective inverse agonist
RO5212773 (EPPTB)^ⁿ	4.5	0	0.94	0.028	−12	0.0009	7.5	0	>5.0

↵^a Simmler et al. (2016).
↵^b Lindemann et al. (2005).
↵^c Sotnikova et al. (2010).
↵^d Luethi et al. (2017).
↵^e Sukhanov et al. (2014).
↵^f Liu et al. (2014).
↵^g Scanlan et al. (2004).
↵^h Coster et al. (2015).
↵ⁱ Hu et al. (2009).
↵^j Revel et al. (2012a).
↵^k Revel et al. (2011).
↵^l Revel et al. (2012b).
↵^m Revel et al. (2013).
↵ⁿ Stalder et al. (2011). IC₅₀ values are presented in lieu of EC₅₀ values.