Compound 9 (DA-0218, 30 nmol intrathecally) is effective against histamine- and lymphoma-induced itch in mice. (A and B) Histamine-induced acute itch after intradermal injection (500 μg) is alleviated by DA-0218. (A) Time course of acute itch. DA-0218 dose had a statistically significant time-dependent effect on itch (repeated measures two-way ANOVA time × dose interaction F[15, 130] = 2.847; P = 0.001; **P = 0.001; ****P < 0.0001). P values are Bonferroni-corrected. (B) Same data presented as the count of scratch bouts over 30 min. (One-way ANOVA F[3, 26] = 5.207; P = 0.006). Post hoc pairwise comparisons show that intrathecal 30 nmol DA-0218 resulted in a statistically significant reduction of histamine-induced scratches in comparison to vehicle. Experimental sample size is n = 6 to 9 mice per group. (C) Lymphoma-induced chronic itch at day 50 is alleviated by intrathecal injection of DA-0218 (repeated measures two-way ANOVA time × treatment interaction F[3, 30] = 5.716; P = 0.003). Post hoc pairwise comparisons show that the effect is present at 1 h (P < 0.0001), 3 h (P = 0.003), and 5 h (P = 0.008), Bonferroni-corrected for four tests. Experimental sample size is n = 6 mice per group.