Table 3. ED₅₀ values and therapeutic windows for SR compounds.

Hot plate (HP), tail flick (TF), % arterial oxygen saturation (O₂) and breath rate (BR, breaths per minute) ED₅₀ values (mg/kg) were calculated from the hyperbolic fits (maximum value shared at 100%) of the area-under-the-curve analysis of dose response studies performed in male C57BL6/J mice (Figure S4 (A–D)) for the 1 hour period following drug treatment. The ratios of ED₅₀ values for respiratory suppression over antinociception are represented by the therapeutic windows. Mean and 95% confidence intervals are provided. %MPE for all assays are defined on the lower limit by the baseline (BL) response and an upper limit (max, 100%) designed to limit the severity of each assay: Hot Plate (52°C): BL: 6.78 ± 0.14 sec, max: 20 sec; Tail Flick (49°C): BL: 2.95 ± 0.07 sec, max: 30 sec; %O₂: BL: 95.11 ± 0.12 %, max: 70%; Breath Rate: BL: 165.0 ± 0.2, max: 75). See also: Figure S4 for the behavioral dose response curves and Figure 3C for a graphical representation of the therapeutic windows.

Agonist	ED50 (95% confidence intervals)				Therapeutic Window
	Hot Plate	Tail Flick	%O2 Saturation	Breath Rate	O2/HP	O2/TF	BR/HP	BR/TF
Fentanyl	0.24 (0.16 to 0.32)	0.14 (0.07 to 0.20)	0.71 (0.60 to 0.85)	0.52 (0.37 to 0.67)	3	5	2	4
SR-11501	4.6 (2.9 to 6.3)	11 (5.6 to 16)	18 (13 to 27)	7.6 (4.6 to 11)	4	2	2	1
Morphine	5.9 (4.4 to 7.5)	3.8 (2.5 to 5.2)	79 (62 to 104)	33 (23 to 42)	13	21	5	9
SR-14969	1.7 (0.88 to 2.5)	2.3 (1.4 to 3.2)	21 (16 to 29)	20 (9.8 to 30)	13	9	12	9
SR-14968	0.44 (0.31to 0.57)	0.61 (0.32 to 0.89)	14 (11 to 18)	11 (5.6 to 17)	31	23	28	20
SR-15098	12 (9.5 to 15)	13 (8.9 to 18)	538 (276 to 3359)	174 (70 to 277)	44	40	14	13
SR-15099	8.4 (6.2 to 11)	7.4 (4.9 to 9.9)	560 (260 to >5000)	206 (25 to 386)	67	75	28	28
SR-17018	6.9 (4.7 to 9.1)	7.7 (4.1 to 11.3)	719 (278 to >5000)	197 (24 to 370)	105	93	29	26