Guanabenz

Guanabenz (WY 8678) is an α2 adrenergic receptor agonist that is used as an antihypertensive agent, also has been proposed to exert protective effects against misfolding by interfering with eIF2α-P dephosphorylation through selective disruption of a PP1-PPP1R15A holophosphatase complex; also has antiparasitic activity against replicative stages of Toxoplasma.Multiple Sclerosis Phase 1 Clinical (In Vitro) :Guanabenz hydrochloride (0.5-50 μM, 24 h) is treated with increasing concentrations for 24 hours not affect cell viability.Guanabenz hydrochloride (0.5-50 μM, 24 h) alone not affects the UPR targets, neither on mRNA or protein level nor the phosphorylation status of eIF2a. Guanabenz also not induces GADD34 or the constitutively active form CReP.Guanabenz hydrochloride (0.5-50 μM, 24 h) alone not induces ER stress in neonatal rat cardiomyocytes. (In Vivo) :Guanabenz hydrochloride (5 mg/kg/day; i.p.; for 3 weeks) can reproducibly reduce brain cyst burden.Guanabenz hydrochloride (5 mg /kg/d, i.p., oral; 10 mg/kg/d, gavage; for 3 weeks) reverses Toxoplasma-induced hyperactivity in latently infected mice.Guanabenz hydrochloride (100 and 320 μg/kg and 1 mg/kg, i.v., over a period of 5 min at intervals of 40 min) reduces sympathetic outflow, heart rate and blood pressure in debuffered cats.