Table 6

TRPV1 antagonists: their potencies at different modes of activation of rat TRPV1 in vitro and their effects upon systemic administration on deep T_b in rats in vivo

Name	In Vitro: IC₅₀ for Different Activation Modes			In Vivo: Effect on Deep T_b
Name	CAP (500 nM)	pH (5.0)	Heat (45°C)	Dose	Route	Effect
	nM	nM	nM	mg/kg
A-425619	10 ± 2^a	13 ± 2^a	58 ± 4^a	4–100	p.o.	↑^a^b
A-889425	335^c	—	—	4–13	p.o.	↑^c
				2	i.v.	↑^c
ABT-102	1^d	16^d	100^d	1–10	p.o.	↑^e
AMG0347	0.7 ± 0.1^f	0.8 ± 0.3^f	0.2 ± 0.1^f	0.01–0.5	i.v.	↑^f
AMG1629	0.6 ± 0.4^a	1 ± 0^a	0.2 ± 0.0^a	3	p.o.	↑^a
AMG2820	1 ± 0^a	>4000^a	23 ± 6^a	3	i.v.	↑^a
AMG3731	6 ± 5^a	7 ± 1^a	5 ± 0^a	3–10	p.o.	↑^a
AMG 517	1 ± 1^g	0.5 ± 0.2^g	2 ± 1^g	0.1–3	p.o.	↑^g^h
	0.9 ± 0.8^h	0.5 ± 0.2^h	—	0.1	i.v.	↑ⁱ
AMG7988	14 ± 2^a	>4000^a	360 ± 97^a	3	i.v.	↑^a
AMG8163	0.6 ± 0.3^a^j	0.6 ± 0.3^a^j	0.2 ± 0.1^a^j	0.1–10	p.o.	↑^a^g
				0.3	i.v.	↑^j
AMG8563	3 ± 1^j	>4000^j	2 ± 0^j	3	i.v.	↑^j
AMG9810	79 ± 9^a	349 ± 66^a	9 ± 1^a	30	i.p.	↑^a
	86 ± 39^k	294 ± 192^k	21 ± 17^k
BCTC	0.4 ± 0.3^a	0.5 ± 0.6^a	0.1 ± 0.0^a	3	i.v.	↑^a
	0.5 ± 0.1^k	0.7 ± 0.4^k	0.6 ± 0.2^k
Comp. 41	102 ± 12^l	16 ± 4^l	—	30	p.o.	↑^l
Comp. G	1 ± 0^a	1 ± 0^a	2 ± 0^a	30	p.o.	↑^a
Comp. H	18 ± 3^a	70 ± 5^a	16 ± 9^a	30	p.o.	↑^a
AMG7905	39 ± 17^j	N.A.	N.A.	0.3–30	p.o.	↓^j
AMG8562	2 ± 1^j	N.A.	>4000^j	1–30	p.o.	↓^j
				3	i.v.	↓^j
JYL 1421	8^a	N.A.	>4000^j	3–100	p.o.	↕^a
	37^m	—	—	1–10	i.p.	↕^m

N.A., not applicable (IC₅₀ for the marked activation mode could not have been measured, because potentiation was observed instead of inhibition); —, IC₅₀ for this mode of activation was not determined; ↑, an increase in deep T_b; ↓, a decrease in deep T_b; ↕, no effect.
↵a Gavva et al. (2007b). pH of 5.5 was used in this study of A-425619 in which no TRPV1 inhibition occurred at pH of 5.0.
↵b Mills et al. (2008).
↵c McGaraughty et al. (2009). CAP concentration used in this study was not specified.
↵d Surowy et al. (2008). CAP concentration of 1 μM, pH of 5.5, and temperature of 50°C were used in this study.
↵e Honore et al. (2009).
↵f Steiner et al. (2007).
↵g Gavva et al. (2007a).
↵h Tamayo et al. (2008).
↵i Gavva et al. (2008).
↵j Lehto et al. (2008).
↵k Gavva et al. (2005b).
↵l Swanson et al. (2005). CAP concentration of 100 nM and a pH range of 5.8 to 6.0 were used in this study.
↵t Suh et al. (2003).