TABLE 2

Affinities of the H₃R for agonists and antagonists

Data reported as Ki were converted to pKi. For recombinant receptors all values refer to the H₃R of 445 aa.

	pKi
	Rat	Mouse	Guinea Pig	Monkey	Dog	Human
Imidazole-Containing Agonists
Histamine	Native
	8.27^{^a}	7.92 ± 0.54 (high)^{^b}	7.58^{^a}	7.88^{^c}	8.50 ± 0.08^{^d}	8.59 ± 0.08^{^d}
	8.28^{^e}	6.09 ± 0.61 (low)^{^b}	8.18 ± 0.15^{^d}			8.63^{^f}
	7.92^{^g}					8.08^{^c}
	8.29 ± 0.03^{^d}
	8.20 ± 0.10^{^e}
	8.30^{^f}
	8.13^ⁱ
		7.82^{^j}
	Recombinant
	7.87^{^g}			8.78 ± 0.10^{^k}		7.81^{^g}
	8.57^{^f}					8.58^{^f}
	7.69^{^l}					7.88^{^l}
	5.70 ± 0.15^{^m}					8.20 ± 0.04^ⁿ
	7.89 ± 0.07^ⁿ					8.55 ± 0.01^{^k}
						8.00 ± 0.10^{^o}
						8.03 ± 0.06^{^p}
						8.30 ± 0.10^{^q}
						8.60 ± 0.00^{^r}
						8.50^{^s}
						8.40 ± 0.20^{^t}
RAMH	Native
	8.88^{^a}^,^{^e}	7.91 ± 0.09 (high)^{^b}	8.49^{^a}	8.50^{^c}	8.93 ± 0.19^{^d}	9.15 ± 0.06^{^d}
	8.82^{^g}	6.67 ± 0.21 (low)^{^b}	8.63 ± 0.25^{^d}			8.82^{^c}
	8.71 ± 0.08^{^d}		9.48 ± 0.16^{^u}			9.16 ± 0.07^{^v}
	8.95^ⁱ		10.07 ± 0.16^{^u}
	8.71 ± 0.08^{^v}

	Recombinant
	8.72^{^g}	8.40^{^j}		9.55 ± 0.04^{^k}		8.67^{^g}
	8.44^{^l}					8.56^{^l}
	6.40 ± 0.20^{^m}					8.91 ± 0.07^ⁿ
	8.62 ± 0.07^ⁿ					9.41 ± 0.05^{^k}
	9.35 ± 0.20^{^v}					8.20 ± 0.10^{^o}
						8.36 ± 0.07^{^p}
						8.92 ± 0.11^{^q}
						9.00 ± 0.10^{^r}
						9.16 ± 0.08^{^v}
						8.56^{^w}
SAMH	Native
	7.30^{^a}	5.93 ± 0.04^{^b}	7.30^{^a}	7.69^{^c}	7.79 ± 0.11^{^d}	7.49^{^c}
	7.33 ± 0.06^{^d}		7.63 ± 0.18^{^d}			8.33 ± 0.18^{^d}
	7.11^ⁱ

	Recombinant					7.20 ± 0.10^{^o}
						7.60 ± 0.20^{^r}
NAMH	Native
	8.92^{^g}		8.67 ± 0.27^{^d}	8.76^{^c}	9.15 ± 0.09^{^d}	9.41 ± 0.06^{^d}
	8.78 ± 0.13^{^d}		9.99 ± 0.24^{^u}			9.08^{^c}
	9.15^ⁱ		10.31 ± 0.24^{^u}

	Recombinant					8.61^{^g}
	8.82^{^g}					9.22 ± 0.03^ⁿ
	8.70 ± 0.09^ⁿ	8.95^{^j}				8.40 ± 0.10^{^o}
						9.00 ± 0.10^{^r}
						9.80^{^s}
Immepip	Native
	9.30^{^g}	9.50 ± 0.66 (high)^{^b}	8.68 ± 0.34^{^d}		9.25 ± 0.06^{^d}	9.58 ± 0.06^{^d}
	8.99 ± 0.20^{^d}	7.48 ± 0.33 (low)^{^b}

	Recombinant
	8.85^{^g}	9.79^{^j}				8.79^{^g}
	7.50 ± 0.08^{^m}					9.30 ± 0.10^{^o}
						9.32 ± 0.04^p
						9.51 ± 0.03^q
						9.40 ± 0.10^r
						9.70^s
						9.40 ± 0.10^{^t}
						9.30^{^x}
Imetit	Native
	10.00^{^e}	9.09 ± 0.18 (high)^{^b}	8.99 ± 0.25^{^d}	9.01^c	9.31 ± 0.06^{^d}	9.67 ± 0.06^{^d}
	10.00^{^g}	7.02 ± 0.60 (low)^{^b}				9.50^{^c}
	9.46 ± 0.10^{^d}					9.79 ± 0.07^{^v}
	9.82^ⁱ
	9.53 ± 0.09^{^v}

	Recombinant	9.69^{^j}
	9.69^{^g}			9.84 ± 0.03^{^k}		9.22^{^g}
	9.38 ± 0.08^ⁿ					9.20 ± 0.05^ⁿ
	10.11 ± 0.10^{^v}					9.59 ± 0.09^{^k}
						8.80 ± 0.10^{^o}
						9.23 ± 0.19^{^q}
						9.40 ± 0.10^{^r}
						9.70^{^s}
						9.59 ± 0.09^{^v}
Impentamine	Recombinant
	6.90 ± 0.06^{^m}					8.84 ± 0.06^ⁿ
	10.11 ± 0.05^ⁿ					8.30 ± 0.10^{^o}
						8.29 ± 0.14^{^p}
						8.50 ± 0.10^{^r}
Proxyfan	Native
	8.51 ± 0.05^{^v}		8.32 ± 0.13^{^u}			8.38 ± 0.13^{^v}
			8.80 ± 0.23^{^u}
	Recombinant
	8.53^{^l}					8.56^{^l}
	8.08 ± 0.10^ⁿ					7.90 ± 0.10^{^o}
	8.62 ± 0.10^{^v}					8.35 ± 0.06^{^v}
						8.40 ± 0.20^{^r}
						7.87 ± 0.07^ⁿ
VUF 5296	Native
	7.60 ± 0.10^h

	Recombinant
						7.17 ± 0.09^{^p}
VUF 5297	Native
	8.76 ± 0.10^{^e}

	Recombinant
						8.03 ± 0.08^{^p}
Methimepip	Recombinant
						9.00 ± 0.10^{^o}
						9.00 ± 0.10^{^x}
Imidazole-Containing Antagonists	pKi
Thioperamide	Native
	8.67^{^a}	8.37 ± 0.12^{^b}	8.69^{^a}	6.61^{^c}	8.17 ± 0.15^{^d}	7.13 ± 0.06^{^d}
	7.99^{^g}	8.30 ± 0.15^{^y}	8.34 ± 0.12^{^d}		7.91 ± 0.10^{^y}	7.21^{^f}
	8.10 ± 0.06^{^d}		8.69 ± 0.05^{^u}		8.17 ± 0.12^{^aa}	6.69^{^c}
	8.12^{^f}		9.08 ± 0.13^{^u}			7.18 ± 0.01^{^aa}
	8.39^ⁱ		8.34 ± 0.11^{^aa}
	8.85^z
	8.48 ± 0.01^{^y}
	8.15 ± 0.06^{^aa}

	Recombinant
	8.37^{^g}	8.49 ± 0.05^{^y}		7.19 ± 0.03^{^k}		7.23^{^g}
	8.49^{^f}					7.13^{^f}
	8.18^{^l}					7.22^{^l}
	7.20 ± 0.08^{^m}					7.34 ± 0.04^ⁿ
	7.94 ± 0.04^ⁿ					7.24 ± 0.06^{^k}
	8.62 ± 0.06^{^y}					7.30 ± 0.10^{^o}
	8.44 ± 0.07^{^aa}					7.34 ± 0.13^{^q}
	8.40 ± 0.20^{^bb}					7.70 ± 0.20^{^r}
	8.44 ± 0.07^{^cc}					7.70^{^s}
						6.90 ± 0.10^{^t}
						7.85^{^w}
						7.12 ± 0.10^{^y}
						7.14 ± 0.06^{^aa}
						7.40 ± 0.33^{^bb}
						7.14 ± 0.06^{^cc}
Ciproxifan	Native
	9.15 ± 0.05^{^d}	9.10 ± 0.16^{^y}	8.70 ± 0.08^{^d}		8.20 ± 0.08^{^d}	6.99 ± 0.08^{^d}
	9.18^{^f}		8.76 ± 0.07^{^dd}		7.46 ± 0.10^{^y}	7.04^{^f}
	9.22 ± 0.05^{^v}				8.24 ± 0.06^dd	7.05 ± 0.07^{^v}
	8.91 ± 0.04^{^y}					6.72 ± 0.14^{^y}
	9.20 ± 0.04^{^dd}					7.05 ± 0.06^{^dd}

	Recombinant
	9.36^{^f}	9.08 ± 0.08^{^y}		7.18 ± 0.05^{^k}		7.20^{^f}
	8.40^{^l}					7.33^{^l}
	8.87 ± 0.08^ⁿ					7.03 ± 0.12^ⁿ
	9.38 ± 0.07^{^v}					7.20 ± 0.04^{^k}
	9.29 ± 0.05^{^y}					7.17 ± 0.04^{^q}
	9.29 ± 0.09^{^cc}					7.40 ± 0.10^{^r}
	9.29 ± 0.09^{^dd}					7.20 ± 0.04^{^v}
						7.02^{^w}
						6.96 ± 0.06^{^y}
						7.20 ± 0.05^{^cc}
						7.20 ± 0.05^{^dd}
Iodoproxyfan	Native
	9.69^ⁱ	8.86 ± 0.16^{^b}	9.76 ± 0.23^{^u}
			10.00 ± 0.09^{^u}

	Recombinant
						9.20 ± 0.10^{^o}
Clobenpropit	Native
	9.30^{^g}	9.28 ± 0.16^{^b}	9.65 ± 0.22^{^d}	8.65^{^c}	10.09 ± 0.13^{^d}	9.08 ± 0.13^{^d}
	9.38 ± 0.08^{^d}	9.57 ± 0.09^{^y}	9.65 ± 0.20^{^aa}		9.84 ± 0.12^{^y}	8.24^c
	9.31^ⁱ				10.09 ± 0.11^{^aa}	9.11 ± 0.11^{^v}
	9.45 ± 0.08^{^v}					9.11 ± 0.11^{^y}
	9.53 ± 0.11^{^y}					9.11 ± 0.12^{^aa}
	9.45 ± 0.08^{^aa}

	Recombinant
	9.39^{^g}	9.50^{^j}		9.72 ± 0.10^{^k}		9.22^{^g}
	8.85^{^l}	9.70 ± 0.08^{^y}				8.61^{^l}
	8.30 ± 0.02^{^m}					9.34 ± 0.06^ⁿ
	9.11 ± 0.06^ⁿ					9.43 ± 0.03^{^k}
	9.82 ± 0.07^{^v}					8.60 ± 0.10^{^o}
	9.59 ± 0.09^{^y}					8.79 ± 0.08^{^q}
	9.75 ± 0.01^{^aa}					9.30 ± 0.20^{^r}
						9.30^{^s}
						9.47 ± 0.04^{^v}
						9.23^{^w}
						9.47 ± 0.19^{^y}
						9.44 ± 0.04^{^aa}
Iodophenpropit	Native
	9.23 ± 0.10^{^d}	9.24 ± 0.21^{^b}	9.39 ± 0.21^{^d}		9.59 ± 0.09^{^d}	8.45 ± 0.14^{^d}
			10.08 ± 0.11^{^u}
			9.96 ± 0.23^{^u}


	Recombinant					8.20 ± 0.10^{^o}
						9.10 ± 0.20^{^r}
SCH 79687	Native
	8.72^{^ee}		7.88^{^ee}
VUF 5681	Recombinant
						8.35 ± 0.11^{^p}
						8.90 ± 0.30^{^r}
Burimamide	Native
	8.18 ± 0.15^{^d}	6.28 ± 0.2^{^b}	8.27 ± 0.05^{^d}		8.42 ± 0.13^{^d}	8.34 ± 0.21^{^d}
	7.16ⁱ

	Recombinant
						7.90 ± 0.10^{^o}
Non-imidazole antagonists	pKi
JNJ-5207852	Recombinant
	8.90 ± 0.17^{^bb}					9.24 ± 0.21^{^bb}
ABT-239	Native
	7.92 ± 0.11^{^y}	7.96 ± 0.08^{^y}	8.59 ± 0.12^{^f}^{^f}		8.61 ± 0.20^{^y}	8.34 ± 0.06^{^ff}
	8.49 ± 0.04^{^ff}				8.41 ± 0.07^{^ff}

	Recombinant
	8.52 ± 0.08^{^y}	8.42 ± 0.07^{^y}				9.51 ± 0.10^{^y}
	8.87 ± 0.04^{^cc}					9.35 ± 0.04^{^cc}
	8.91 ± 0.04^{^ff}					9.35 ± 0.04^{^ff}
NNC 38-1049	Recombinant
	8.29^{^gg}					8.92^{^w}
A-331440	Native
	7.66^{^f}					7.64^{^f}
	7.73 ± 0.08^{^hh}					7.63 ± 0.05^{^hh}

	Recombinant
	8.20^{^f}			8.71 ± 0.06^k		8.48^{^f}
	8.23 ± 0.04^{^hh}					8.45 ± 0.05^{^k}
						7.75 ± 0.04^{^q}
						8.00^{^r}
						8.45 ± 0.05^{^hh}
A-349821	Native
	9.12 ± 0.14^{^hh}					9.37 ± 0.08^{^hh}

	Recombinant
	8.78 ± 0.12^{^cc}			9.67 ± 0.14^{^k}		9.55 ± 0.09^{^k}
	8.78 ± 0.12^{^hh}					9.20 ± 0.10^{^r}
						9.39 ± 0.08^{^cc}
						9.39 ± 0.08^{^hh}
UCL1972	Native
	7.41^ⁱⁱ
GSK189254	Native
	8.51 ± 0.11^{^y}	8.89 ± 0.13^{^y}			8.83 ± 0.09^{^y}	9.59 ± 0.15^{^y}

	Recombinant
	9.17 ± 0.09^{^y}	8.76 ± 0.06^{^y}				9.90 ± 0.18^{^y}
Pitolisant	Native
		7.85^{^j}^{^j}
	Recombinant
						8.56^{^j}^{^j}

SAMH, S-α-methylhistamine.
↵^a Arrang et al., 1987a.
↵^e Garbarg et al., 1992.
↵^g Lovenberg et al., 2000.
↵^d Ireland-Denny et al., 2001.
^e De Esch et al., 1999.
↵^f Hancock et al., 2004a.
↵ⁱ Ligneau et al., 1994.
↵^l Ligneau et al., 2000.
↵^m Drutel et al., 2001.
↵ⁿ Schnell et al., 2010.
↵^b Jansen et al., 2000.
↵^j Chen et al., 2003.
↵^c West et al., 1999.
↵^k Strakhova et al., 2008.
↵^o Lim et al., 2005.
↵^p Kitbunnadaj et al., 2003.
↵^q Flores-Clemente et al., 2013.
↵^r Bongers et al., 2007b.
↵^s Lovenberg et al., 1999.
↵^t Bongers et al., 2007c.
↵^v Krueger et al., 2005.
↵^u Harper et al., 1999.
↵^w Zaragoza et al., 2004.
↵^x Kitbunnadaj et al., 2005.
↵^z Sánchez-Lemus and Arias-Montaño, 2004.
↵^y Medhurst et al., 2007.
↵^aa Esbenshade et al., 2003.
↵^bb Barbier et al., 2004.
↵^cc Cowart et al., 2005.
↵^dd Esbenshade et al., 2004.
↵^ee McLeod et al., 2003.
↵^ff Esbenshade et al., 2005.
↵^gg Malmlöf et al., 2005.
↵^hh Hancock et al., 2004b.
↵ⁱⁱ Ganellin et al., 1998.