Table 1

Mean ED₅₀ values in mg/kg (±S.E.M.) for morphine or heroin administered alone or after pretreatment with naltrexone or 3-methoxynaltrexone in monkeys trained in a warm water tail-withdrawal assay (n = 3) and monkeys trained to discriminate heroin (n = 3)

Treatment	Antinociception ED₅₀	Substitution ED₅₀	Rate Suppression ED₅₀
Naltrexone
Morphine alone	5.82 (2.02)	0.87 (0.27)	2.28 (0.82)
⁺0.0032 Naltrexone	11.37 (2.50)	2.52 (0.68)^1-150	5.52 (0.89)^1-150
⁺0.01 Naltrexone	43.12 (0.53)^1-150	6.79 (0.21)^1-150	12.57 (2.69)^1-150
⁺0.032 Naltrexone	72.52 (6.55)^1-150	16.69 (3.22)	24.59 (5.54)^1-150
Heroin alone	0.30 (0.06)	0.05 (0.02)	0.14 (0.03)
⁺0.0032 Naltrexone	0.30 (0.13)	0.11 (0.05)	0.18 (0.04)
⁺0.01 Naltrexone	1.33 (0.01)^1-150	0.18 (0.04)^1-150	0.45 (0.16)^1-150
⁺0.032 Naltrexone	1.70 (0.25)^1-150	1.01 (0.55)	0.87 (0.24)^1-150
⁺0.1 Naltrexone	7.16 (0.26)^1-150	N.T.	N.T.
3-Methoxynaltrexone
Morphine alone	5.82 (2.02)	0.88 (0.26)	3.33 (1.82)
⁺0.1 3-Methoxynaltrexone	4.90 (0.88)	N.T.	N.T.
⁺0.32 3-Methoxynaltrexone	22.39 (0.74)^1-150	2.77 (1.92)	6.27 (0.67)
⁺1.0 3-Methoxynaltrexone	31.90 (7.90)^1-150	6.31 (3.85)^1-151	18.14 (3.97)^1-150
⁺3.2 3-Methoxynaltrexone	62.13 (10.27)^1-150	N.D.	N.D.
Heroin alone	0.30 (0.06)	0.05 (0.02)	0.16 (0.01)
⁺0.32 3-Methoxynaltrexone	0.50 (0.03)^1-150	0.13 (0.04)	0.33 (0.05)
⁺1.0 3-Methoxynaltrexone	1.66 (0.24)^1-150	0.37 (0.15)^1-151	0.63 (0.15)^1-150
⁺3.2 3-Methoxynaltrexone	1.85 (0.25)^1-150	N.D.	N.D.

N.D., not determined; N.T., not tested.
↵1-150 Significantly different from morphine or heroin alone (pvalues < 0.05).
↵1-151 Data not submitted to statistical analyses (see text). However, 1.0 mg/kg 3-methoxynaltrexone produced rightward or downward shifts in heroin and morphine substitution dose-effect curves in all three monkeys.