Figures & data
Notes: aCentral histamine H3R assay in vivo after po administration to mice, n=3.30,59–62 b[125I]Iodoproxyfan binding assay at human H3R stably expressed in CHO-K1 cells, n=3.30,63,64 c[3H]Histamine binding assay performed with cell membrane preparation of Sf9 cells transiently expressing the human histamine H4R and co-expressed with Gαi2 and Gβ1γ2 subunits, n=3.31,65–67 d[3H]Pyrilamine binding assay performed with cell membrane preparation of CHO-hH1R cells stably expressing the human H1R, n=3.Citation68–Citation70
Abbreviations: H3R, H3 receptor; PIT, pitolisant; p.o., peroral.
Abbreviations: H3R, H3 receptor; PIT, pitolisant; p.o., peroral.
Notes: (A) The figure shows the protective effects of PHT (10 mg/kg, i.p.), PIT (10 mg/kg, i.p.), and test compounds 3–14 (10 mg/kg, i.p.) on the duration of THLE induced in the MES model in rats. Values are mean ± SEM (n=7). *P<0.005 vs the saline-treated group. **P<0.001 (B) 1: Dose-dependent effect of H3R ligand 14 (5, 10, and 20 mg/kg, i.p.) on duration of THLE induced in the MES model in rats; 2: Effect of PYR (10 mg/kg, i.p.) and ZOL (10 mg/kg, i.p.) pretreatment on the protection provided by H3R 14 (10 mg/kg, i.p.) against MES-induced convulsions. Each value represents mean ± SEM (n=7). *P<0.05 vs (saline)-treated group. **P<0.001 vs (saline)-treated group. #P<0.05 vs (5 mg)-treated group.
Abbreviations: H3R, H3 receptor; MES, maximal electroshock; PHT, phenytoin; PIT, pitolisant; THLE, tonic hind limb extension; PYR, pyrilamine; ZOL, zolantidine; SEM, standard error of the mean; SAL, saline.
Abbreviations: H3R, H3 receptor; MES, maximal electroshock; PHT, phenytoin; PIT, pitolisant; THLE, tonic hind limb extension; PYR, pyrilamine; ZOL, zolantidine; SEM, standard error of the mean; SAL, saline.
Notes: (A) VPA (100 mg/kg, i.p.), PIT (10 mg/kg, i.p.), and compounds 3–14 (10 mg/kg, i.p.) were injected 30 min before PTZ (60 mg/kg, i.p.) treatments. Effects shown are expressed as score of seizures after 10, 20, and 30 min of PTZ injection. Data are expressed as the mean ± SEM (n=7). *P<0.05 vs the (PTZ–saline)-treated group. #Full protection. (B) Dose-dependent effect of H3R ligands 4 and 6 (A, B, and C in a dose of 5, 10, and 20 mg/kg, i.p. respectively) on the convulsion score induced in the PTZ model in rats. Effect of PYR (10 mg/kg, i.p.) and ZOL (10 mg/kg) pretreatment on the protection provided by H3R ligand 4 (10 mg/kg, i.p.) against PTZ-induced convulsions. Each value represents mean ± SEM (n=7). *P<0.05 vs (PTZ–saline)-treated group. #Full protection.
Abbreviations: H3R, H3 receptor; PTZ, pentylenetetrazole; VPA, valproic acid; PIT, pitolisant; SEM, standard error of the mean; PYR, pyrilamine; ZOL, zolantidine.
Abbreviations: H3R, H3 receptor; PTZ, pentylenetetrazole; VPA, valproic acid; PIT, pitolisant; SEM, standard error of the mean; PYR, pyrilamine; ZOL, zolantidine.
Notes: (A) VPA (300 mg/kg, i.p.), PIT (10 mg/kg, i.p.), and compounds 3–14 (10 mg/kg, i.p.) were injected 30 min before STR (3.5 mg/kg, i.p.) treatments. Values are expressed as the mean ± SEM (n=7). *P<0.001 vs (STR–saline)-treated group. #Full protection. (B) Dose-dependent effect of H3R ligand 14 (A, B, and C in a dose of 5, 10, and 20 mg/kg, i.p., respectively) on the convulsion score induced in the STR model in rats, and effect of PYR (10 mg/kg, i.p.) and ZOL (10 mg/kg) pretreatment on the protection provided by H3R ligand 14 (10 mg/kg, i.p.) against STR-induced convulsions. Each value represents mean ± SEM (n=7). *P<0.05 vs (PTZ–saline)-treated group. **P<0.001. #Full protection.
Abbreviations: H3R, H3 receptor; STR, strychnine; VPA, valproic acid; PIT, pitolisant; SEM, standard error of the mean; PYR, pyrilamine; ZOL, zolantidine; PTZ, pentyl-enetetrazole.
Abbreviations: H3R, H3 receptor; STR, strychnine; VPA, valproic acid; PIT, pitolisant; SEM, standard error of the mean; PYR, pyrilamine; ZOL, zolantidine; PTZ, pentyl-enetetrazole.
Notes: The darker color of the marked functional group indicates its higher probability to be involved in the metabolic pathway. The blue circle marks the site of H3R ligand involved in metabolism with the highest probability calculated by MetaSite method.
Abbreviation: H3R, H3 receptor.
Abbreviation: H3R, H3 receptor.
Abbreviations: KE, ketoconazole; CYP, cytochrome P450; QD, quinidine; DX, doxorubicin; HEK, human embryonic kidney.
Note: Assay was performed in triplicates.
Abbreviations: H3R, H3 receptor; NQNO, nonyl-4-hydroxyquinoline-N-oxide.
Abbreviations: H3R, H3 receptor; NQNO, nonyl-4-hydroxyquinoline-N-oxide.