The results are Dinaciclib in vivo expressed as mean ± SEM of a group of 8–18 mice. A—one-way ANOVA showed significant changes in the numer of writhing episodes of mice after the administration of the compound 3a (F 4.43 = 5.627, p = 0.001), 3d (F 4.46 = 5.537, p = 0.001), 3g (F 4.47 = 6.281, p < 0.001). Post-hoc Tukey’s test confirmed a significant reduction in the writhing episodes of mice after
the administration of the compound 3a in the dose of 0.1, 0.05 ED50 (p < 0.05), and 0.025 ED50 (p < 0.001), 3d—0.1, 0.05, 0.025 ED50 (appropriately p < 0.01, p < 0.05, p < 0.01), 3g—0.1, 0.05, 0.025 ED50 (p < 0.01, p < 0.05, p < 0.001). B—One-way ANOVA showed significant changes in the numer of writhing episodes of mice after the administration of the PF299 price compound 3n (F 4.38 = 7.204, p < 0.001), 3p (F 5.54 = 7.257, p < 0.0001), and 3s (F .,49 = 14.17, p < 0.0001). Post-hoc Tukey’s test confirmed a significant reduction in the writhing episodes of mice after the Crenigacestat administration of the compound 3n—0.1, 0.05, and 0.025 ED50 (p < 0.001, p < 0.01, p < 0.05), 3p—0.1, 0.05 ED50 (p < 0.001), and 0.025, 0.0125 ED50 (p < 0.05) and 3s—0.1,
0.05 ED50 (p < 0.001), and 0.025 ED50 (p < 0.01) Fig. 7 The influence of the tested compounds on the spontaneous locomotor activity of mice. The results are expressed as mean ± SEM of a group of 6–14 mice. One-way ANOVA showed significant changes in locomotor activity of mice after the administration of the compound 3a (F 3,29 = 5.999, p < 0.01), 3d (F 4,35 = 4.942,
p < 0.01), 3g (F 3,31 = 5.6, p < 0.01), 3l (F 2,25 = 3.361, p = 0.051) and 3n (F 4,37 = 6.596, p < 0.001). Post-hoc Sclareol Tukey’s test confirmed a significant reduction in motility of mice after the administration of the compound 3a in the dose of 0.1 ED50 (p < 0.05) and 0.05 ED50 (p < 0.01), 3d—0.1 ED50 (p < 0.01), 0.05, and 0.025 ED50 (appropriately p < 0.05, p < 0.01), 3g—0.1 ED50 (p < 0.05) and 0.05 ED50 (p < 0.01), 3l—0.1 ED50 (p < 0.05) and 3n—0.1, 0.05, and 0.025 ED50 (p < 0.01) Most of the tested compounds (with the exception of 3p and 3s) significantly decreased spontaneous motility of mice (Fig. 7). The noted effects of 3a and 3g were very strong and persisted up to 0.05 ED50, these of 3d and 3n up to 0.025 ED50 and compound 3l decreased motility only at the dose of 0.1 ED50 (p < 0.05). None of the tested compounds inhibits amphetamine-induced hyperactivity (data not presented). It is necessary to underline that the tested compounds did not exhibit neurotoxicity because used in dose equivalent to 0.1 ED50 they did not disturb motor coordination of mice in the rota-rod test. The only exception was substance 3p, discussed above. The lack of motor-impairing effects is important because it can change the results of other tests (e.g., motility tests) and affecting reliability of the tests results.