Table 1.

Summary of Clonidine–Dexmedetomidine Antinociceptive Interactions

	Probe Drug, Intrathecal, nmol	ED50 Clonidine (95% CI)	ED50 Dexmedetomidine (95% CI)	Interaction
Figure 1, ICR mice	Single drug	3.0 (2.1–3.9)	3.8 (1.3–6.3)
	Clonidine–dexmedetomidine, 1:1 ratio			Synergistic
	Observed combination	0.0045 (0.0001–0.0183)*
	Theoretical additive	1.7 (1.3–2.1)
Figure 2, α2AAR-WT	Single drug	1.2 (0.45–1.9)	1.0 (0.43–1.7)
	Clonidine–dexmedetomidine, 1:1 ratio			Synergistic
	Observed combination	0.18 (0.1–0.26)*
	Theoretical additive	0.54 (0.34–0.74)
Figures 4A and B, α2CAR-WT	Single drug	1.7 (1.3–2.1)	1.9 (1.3–2.5)
	Clonidine–dexmedetomidine, 1:1 ratio			Synergistic
	Observed combination	0.16 (0.11–0.23)*
	Theoretical additive	0.90 (0.73–1.1)
Figures 4C and D, α2CAR-zKO	Single drug	5.3 (4.1–6.5)	4.4 (3.5–5.3)
	Clonidine–dexmedetomidine, 1:1 ratio			Subadditive
	Observed combination	3.6 (2.2–5.0)*
	Theoretical additive	1.71 (1.3–2.1)

^*Significant difference from theoretical additive by Student t test, P < 0.05.

AR = adrenergic receptor; CI = confidence interval; ICR = Institute of Cancer Research; KO = knockout; WT = wild type.