Fig. 6: Improved therapeutic window effects of ‘1350 and ‘4936.

a Open Field test (n = 5 except vehicle n = 10; one-way ANOVAs, ‘1350: F(2, 17) = 9.5, P = 0.002; CP-55,940: F(2, 17) = 13.7, P = 0.003). Asterisks define differences after Dunnett’s multiple comparisons post-hoc correction; vehicle vs. ‘1350, 0.2 mg/kg: P = 0.03; 0.5 mg/kg: P = 0.001; vs. CP-55,940, 0.2 mg/kg: P = 0.0006; 0.5 mg/kg: P = 0.002. b Rotarod test (n = 5 for CP-55,940 0.1, 1.0 mg/kg, ‘1350 0.1, 0.5 mg/kg, ‘4936 0.2, 2.0 mg/kg. n = 10 for CP-55,940 vehicle, 0.2 mg/kg, ‘1350 vehicle, 0.2 mg/kg, and ‘4936 vehicle, 0.5, 1.0 mg/kg; one-way ANOVAs, CP-55,940: F(3, 26) = 5.7, P = 0.04; ‘1350: F(3, 26) = 5.7, P = 0.004; ‘4936: F(4, 35) = 2.7, P = 0.05). Asterisks define differences after Dunnett’s multiple comparisons post-hoc correction; vehicle vs. CP-55,940, 0.1 mg/kg: P = 0.42; 0.2 mg/kg: P = 0.02; 1.0 mg/kg: P = 0.006; vehicle vs. ‘1350, 0.1 mg/kg: P = 0.99; 0.2 mg/kg: P = 0.32; 0.5 mg/kg: P = 0.002; vehicle vs. ‘4936, 0.2 mg/kg: P = 0.99; 0.5 mg/kg: P = 0.71; 1.0 mg/kg: P = 0.4; 2.0 mg/kg: P = 0.02. c Catalepsy test (n = 5 for haloperidol vehicle, 1.0 mg/kg, CP-55,940 0.2, 1.0 mg/kg, ‘1350 vehicle, 0.2, 1.0 mg/kg, and ‘4936 vehicle, 0.2, 0.5, 1.0 mg/kg. n = 10 for haloperidol baseline, CP-55,940 vehicle, 0.5 mg/kg. n = 15 for ‘1350 0.5 mg/kg. n = 20 for haloperidol, CP-55,940 baseline. n = 30 for ‘1350 baseline; one-way ANOVAs, CP-55,940: F(3, 26) = 10.7, P < 0.0001; ‘1350: F(3, 26) = 1.03, P = 0.4; ‘4936: F(4, 29) = 1.04, P = 0.4; two-tailed unpaired t-test, haloperidol: t(8) = 6.2, P = 0.0002). Asterisks define differences between 1 mg/kg compound dose to vehicle after t-test (haloperidol) or Dunnett’s multiple comparisons post-hoc correction; ‘1350: P = 0.29; CP-55,940: P < 0.0001; ‘4936: P = 0.67. d–f Therapeutic windows. a–c represent mean ± SEM; n denotes number of independent animals per group. ns, not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.