LY 393558

LY393558 is a potent and orally active inhibitor of the 5-HT transporter and an antagonist of 5-HT1B and 5-HT1D receptors. LY393558 increase the extracellular levels of 5-HT in mice model frontal cortex. LY393558 can be used for researching depression[1].

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

LY393558 (1-20 mg/kg; p.o., single) raises extracellular levels of 5-HT to 200-250% at 1 mg/kg in guinea pigs model, while levels of 5-HT to approximately 1500% at the highest dose 20 mg/kg[1]. LY393558 (20 mg/kg; p.o., single) completely abolishes the reduction of levels of 5-HT induced by tetrodotoxin (1μM) in guinea pigs model[1]. LY393558 (1-20 mg/kg; p.o., single) significantly increases extracellular levels of 5-HT in rats model[1]. LY393558 (5 mg/kg/day; p.o., 21 days) can still elicit a further increase in extracellular 5-HT in chronic treatment[1]. Animal Model: Female Dunkin Hartley guinea pigs (350-400 g)[1] Dosage: 1-20 mg/kg Administration: p.o., single Result: Extracellular levels of 5-HT reached 200-250% at 1 mg/kg, while levels of 5-HT reached approximately 1500% at the highest dose 20 mg/kg. Animal Model: Female Dunkin Hartley guinea pigs (350-400 g)[1] Dosage: 20 mg/kg Administration: p.o., single Result: Completely abolished the reduction of levels of 5-HT induced by tetrodotoxin (1μM). Animal Model: Male Lister Hooded rats (290-320 g)[1] Dosage: 1-20 mg/kg Administration: p.o., single Result: Significantly increased extracellular levels of 5-HT. Animal Model: Male Lister Hooded rats (290-320 g)[1] Dosage: 5 mg/kg/day Administration: p.o., 21 days Result: Still elicited a further increase in extracellular 5-HT in chronic treatment.

[1]. Mitchell SN, et al. LY393558, a 5-hydroxytryptamine reuptake inhibitor and 5-HT(1B/1D) receptor antagonist: effects on extracellular levels of 5-hydroxytryptamine in the guinea pig and rat. Eur J Pharmacol. 2001;432(1):19-27.