Table 1.

Potency of morphine, oxycodone and SR-17018 in the mouse tail flick assay (49°C warm water tail immersion) under acute and chronic treatment paradigms (means with 95% CI). ED₅₀ are determined with maximum confined to 100% MPE.

Treatment Day 1 to 6	Dose mg/kg/day	Substitution Day 7 to 10	Dose mg/kg/day	Challenge	ED50 (95% CI)	ED50 shift (95% CI)
Morphine	saline	n/a	n/a	morphine	9.7 (8.5 to 10.8)	n/a
	24	n/a	n/a	morphine	18.8 (13.6 to 25.3)	2.1 (1.6 to 2.8)
	48	n/a	n/a	morphine	31.7 (22.7 to 57.8)	3.4 (2.5 to 4.7)
SR-17018	vehicle	n/a	n/a	SR-17018	12.7 (11.6 to 13.7)	n/a
	24	n/a	n/a	SR-17018	20.8 (18.4 to 23.4)	1.7 (1.4 to 1.9)
	48	n/a	n/a	SR-17018	32.4 (30.0 to 36.3)	2.6 (2.2 to 3.0)
SR-17018	vehicle	n/a	n/a	SR-17018	17.3 (15.3 to 19.4)	n/a
females	48	n/a	n/a	SR-17018	32.6 (26.5 to 39.5)	1.9 (1.5 to 2.3)
Morphine	saline	n/a	n/a	SR-17018	10.0 (8.4 to 11.7)	n/a
	24	n/a	n/a	SR-17018	19.9 (16.6 to 23.7)	2.0 (1.6 to 2.5)
SR-17018	vehicle	n/a	n/a	morphine	12.9 (12.0 to 13.9)	n/a
	24	n/a	n/a	morphine	20.9 (17.6 to 24.8)	1.6 (1.4 to 1.9)
Oxycodone	vehicle	n/a	n/a	oxycodone	7.7 (6.4 to 9.2)	n/a
	24	n/a	n/a	oxycodone	16.9 (15.3 to 18.6)	2.2 (1.8 to 2.7)
Morphine	saline	vehicle	0	morphine	12.1 (9.8 to 14.6)	n/a
	vehicle	buprenorphine	2	morphine	37.7 (32.2 to 43.7)	3.1 (2.5 to 3.9)
	48	vehicle	0	morphine	15.4 (14.0 to 16.9)	1.3 (1.1 to 1.6)
	48	SR-17018	48	morphine	27.0 (24.2 to 30.2)	2.3 (1.9 to 2.8)
	48	buprenorphine	2	morphine	44.1 (37.7 to 55.2)	3.7 (2.9 to 4.6)