Dabuzalgron (Ro 115-1240) is an orally active and selective α-1A adrenergic receptor agonist for the treatment of urinary incontinence. Dabuzalgron protects against Doxorubicin-induced cardiotoxicity by preserving mitochondrial function[1].
Dabuzalgron treatment increases ERK phosphorylation in a dose-dependent fashion with an EC50 of 4.8 μM. ERK1/2 activation contributes to the cardioprotective effects of Dabuzalgron[1].Dabuzalgron (10 μM; 4 hours) protects NRVMs from cell death due to Doxorubicin (DOX)[1].Activation of the α1A-AR with Dabuzalgron (10 μM; 4 hours) mitigates the detrimental effects of DOX on mitochondrial membrane potential and abrogates the activation of important elements of the apoptotic response to mitochondrial damage[1]. Western Blot Analysis[1] Cell Line: Neonatal rat ventricular myocytes (NRVMs)
Dabuzalgron (10 μg/kg; oral gavage; twice daily; for 7 days; C57Bl6J wild-type or α1A-AR knockout mice) treatment protects against DOX cardiotoxicity by activating the α1A-AR. Dabuzalgron protects against the reduction in transcripts related to mitochondrial function, up-regulates PGC1α, preserves ATP content, and reduces oxidative stress in the hearts of mice treated with DOX[1]. Animal Model: Male C57Bl6J wild-type (WT) or α1A-AR knockout (AKO) mice (8-12-week-old) injected with Doxorubicin (DOX)[1]
[1]. Beak J, et al. An Oral Selective Alpha-1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity. JACC Basic Transl Sci. 2017 Feb;2(1):39-53.