Table 1.

Comparison of epibatidine and varenicline radioligand binding and antinociception data of 3’-(substituted phenyl)deschloroepibatidine analogs to standard nAChR agonist, partial agonist, and antagonist

Compd a	X	Y	α4β2* [3H]Epibatidine (Ki, nM)b	α7 [125I]iodo MLA (Ki, nM)b	ED 50 mg/kg Tail-Flickc	ED 50 mg/kg Hot-Platec	ED 50 mg/kg Hypothermiac	ED 50 mg/kg Spontaneous Activity c	AD 50 (μg/kg)c
									Tail-Flick	Hot-Plate	Body Temperature
Epibatidine (4)			0.026 ± 0.002	198 ± 4	0.006	0.004	0.004	0.001
6ad			0.020 ± 0.001		0.002
6bd			0.027 ± 0.001
Nicotine (1)			1.5 ± 0.3	670 ± 33	1.3	0.65	1.0	0.5
Varenicline (3)			0.12 ± 0.02	32.5 ± 1.3	11% @ 10	10% @ 10	2.8	2.1	0.2	470	0% @ 10,000
5a	H	H	0.50 ± 0.03	7% @ 50 nM	6% @ 10	30% @ 10	1.5 (1.2–3.3)	0.5 (0.13–2)	300 (100–3000)	10% @ 1000	0% @ 1000
5b	Cl	H	0.21 ± 0.03	>2000	1% @ 10	11% @ 10	2% @ 10	10.5 (8.2–15.5)	0% @ 10	0% @ 10	5% @ 1000
5c	H	Cl	0.17 ± 0.021	>2000	1% @ 20	10% @ 20	0% @ 20	3.8 (0.36–41)	0.01 (0.001–0.1)	0% @ 1000	0% @ 1000
5d	F	H	0.15 ± 0.003	>2000	3% @ 10	13% @ 10	-1.6% @ 10	3.0 (2.2–3.9)	13 (2–70)	10% @ 100	0% @ 1000
5e	H	F	0.20 ± 0.04	>2000	2% @ 10	8% @ 10	0% @ 10	5 (3.2–7.9)	3.1 (0.07–1)	3000 (2500–3600)	0% @ 10
5f	NO2	H	0.34 ± 0.005	>2000	1% @ 10	26% @ 10	2.9 (2.1–3.5)	0.66 (0.1–3.9)	47(0.7–33)	10% @ 100	0% @ 100
5g	H	NO2	0.17 ± 0.009	>2000	5% @ 20	21% @ 20	37.6 (30–45)	4.7 (0.25–8.5)	2.5 (0.4–18)	11,000 (900– 13,300)	0% @ 2000
5h	NH2	H	0.34 ± 0.05	>2000	6% @ 10	10% @ 10	0% @ 10	15% @ 10	1 (0.1–4)	45% @ 2000	0% @ 20
5i	H	NH2	1.16 ± 0.14	>2000	6.3 (3.8–10.3)	5.4 (3.2–9.1)	3.8 (2.8–4.8)	1.5 (0.5–4.5)	NT	NT
5j	H	CH3O	0.43 ± 0.05	>2000	1% @ 10	20% @ 10	0% @ 10	2.9 (0.8–10)	0% @ 10	0% @ 10	0% @ 10
7ae	H	H	0.24	>2000	3% @ 15	4% @ 15	-0.5 °C @ 10	4.7	500	1200
7be	Cl	H	0.044		2% @ 10	7% @ 10	0% @ 10	5% @ 10	0.3	260	0% @ 1000
7ce	F	H	0.073		3% @ 10	14% @ 10	0% @ 10	15% @ 10	12	450	0% @ 1000
7de	H	F	0.029		2% @ 10	15% @ 10	10% @ 10	2	0.5	230	0% @ 100
7ee	H	F	0.087		3.5	3.3	1.8	0.36	5	2% @ 1000	0% @ 1000
7fe	NO2	H	0.009		5% @ 10	10% @ 10	3.5	0.22	3	120	0% @ 1000
7ge	H	NO2	0.053		3% @ 10	20% @ 10	0% @ 10	6.5	0.5	130	5% @ 500
7he	NH2	H	0.095		2% @ 10	10% @ 10	0% @ 10	6	5	1800	0% @ 5000
7ie	H	NH2	0.16		1% @ 10	4% @ 10	0% @ 10	8.5	9	820	5% @ 5000
7je	H	CH3O	0.12		0% @ 10	8% @ 10	0% @ 10	6	8	2000	0% @ 10

^a)All epibatidine analogs with the exception of 5b and 5d were tested as hydrochloride salts and all were racemates.

^b)Data represent means ± SE from at least three independent experimentals.

^c)Results are provided as ED₅₀ or AD₅₀ values (± confidence limits) or as a percent effect at the individual dose.

^d)Taken from reference ⁹.

^e)Data take from reference ¹¹.