SB-357134 is a potent, selective, brain penetrant, and orally active 5-HT6 receptor antagonist. SB-357134 enhances memory and learning and increases seizure threshold in rats[1].
in vivo
SB-357134 dose-dependently inhibits the specific [125I]SB-258585 binding[1].
SB-357134 (0.03-30 mg/kg; 0-24 h; p.o.; single dose) produces a potent and dose-related anticonvulsant effect in the rat MEST model, with a minimum significantly effective dose of 0.1 mg/kg[1].
Chronic administration of SB-357134 (10 mg/kg; p.o.; twice daily; 7 days) significantly shortens path length compared to vehicle and acute administration of SB-357134[1].
Animal Model:
Sprague–Dawley rats[1]
Dosage:
0.03–30 mg/kg
Administration:
0-24 h; p.o.; 0.03–30 mg/kg
Result:
Produced a potent and dose-related anticonvulsant effect in the rat MEST model, with a minimum significantly effective dose of 0.1 mg/kg. Increased seizure threshold up to 123±12% at the highest dose tested of 30 mg/kg. At 10 mg/kg, exhibited a rapid onset of action, significantly increasing seizure threshold from a control value of 21.7 to 26.7 mA at 1 h postdose. Observed Peak activity within 4–6 h postdose. With the exception of an unexplained loss of activity at 12 h, had a long duration of action of 21 h in this model.
Animal Model:
Sprague–Dawley rats[1]
Dosage:
10 mg/kg
Administration:
10 mg/kg; p.o.; twice daily; 7 days
Result:
Significantly shortened path length when administered chronically compared to vehicle and administered acutely.
References
[1] Stean TO, et al. Pharmacological profile of SB-357134: a potent, selective, brain penetrant, and orally active 5-HT(6) receptor antagonist. Pharmacol Biochem Behav. 2002 Apr;71(4):645-54. DOI:10.1016/s0091-3057(01)00742-0
