TABLE 1

ED₅₀ values and potency ratios of fentanyl, nalbuphine, and U69,593 alone and in combination with various doses of epibatidine or varenicline

ED₅₀ values in mg/kg with corresponding 95% confidence limits for fentanyl, nalbuphine, and U69,593 alone and in the presence of various doses of epibatidine or varenicline in 50, 52, and 55°C warm water. Potency ratios are calculated when available with corresponding 95% confidence limits. Increases in antinociceptive potency are considered statistically significant if the 95% confidence limits of the potency ratios of drug alone or in the presence of nicotine does not include 1. PR=Potency Ratio; Var=varenicline; Epi=epibatidine; NA=not available.

Drug	50°C		52°C		55°C
	ED₅₀	PR	ED₅₀	PR	ED₅₀	PR
	(95% CL)	(95% CL)	(95% CL)	(95% CL)	(95% CL)	(95% CL)

Fentanyl	0.001		0.002		0.003
	(0.0002–0.007)		(0.0008–0.007)		(0.001–0.006)
+0.032 Var	0.001	0.9	0.002	1.4	0.004	0.7
	(0.0002–0.005)	(0.2–4.3)	(0.0005–0.006)	(0.4–5.3)	(0.002–0.008)	(0.2–2.4)
+0.00056 Epi	0.0007	1.5	0.001	2.1	0.004	0.7
	(0.0003–0.001)	(0.4–6.5)	(0.0004–0.003)	(0.7–6.5)	(0.001–0.009)	(0.2–2.6)
Nalbuphine	1.2		1.6		NA
	(0.28–5.0)		(0.26–10)
+0.032 Var	0.15	7.7	0.25	6.3	NA	NA
	(0.041–0.51)	(1.9–31)	(0.019–3.2)	(0.9–46)
+0.00056 Epi	0.018	74	0.021	62	NA	NA
	(0.0011–0.28)	(49–113)	(0.0076–0.056)	(16–242)
U69,593	0.033		0.037		0.068
	(0.012–0.087)		(0.025–0.054)		(0.031–0.15)
+0.00056 Epi	0.006	5.1	0.013	2.7	0.018	3.7
	(0.003–0.013)	(2–13)	(0.007–0.027)	(1.2–6)	(0.007–0.047)	(1.3–11)