Description
Bumetanide is a loop diuretic that is clinically used to treat congestive heart failure. Bumetanide exhibits natriuretic activity, inhibiting Na+/K+/2Cl- symporter 1 (NKCC1) and K+/Ca2+ co-transporter 2 (KCC2), decreasing fluid secretion and Na+/K+ transport. Bumetanide also exhibits anxiolytic, neuroprotective, andantiepileptic/anticonvulsant activities. Bumetanide induces hyperpolarization in kidney cells, increasing whole-cell conductance and intracellular Ca2+ levels. In animal models, bumetanide decreases conditioned anxiety in contextual fear and startle assays. In injured neurons, this compound inhibits upregulation of low-affinity NGF/pan-neurotrophin receptor p75NTR, preventing cell death. Additionally, bumetanide’s inhibition of NKCC1 co-transporters in neurons alters GABA signaling, inhibiting seizure-induced accumulation of Cl- and facilitation of recurrent seizures in vivo.
References
Wang T, Yang YQ, Karasawa T, et al. Bumetanide hyperpolarizes madin-darby canine kidney cells and enhances cellular gentamicin uptake by elevating cytosolic Ca(2+) thus facilitating intermediate conductance Ca(2+)--activated potassium channels. Cell Biochem Biophys. 2013 Apr;65(3):381-98. PMID: 23109177.
Krystal AD, Sutherland J, Hochman DW. Loop diuretics have anxiolytic effects in rat models of conditioned anxiety. PLoS One. 2012;7(4):e35417. PMID: 22514741.
Shulga A, Magalhães AC, Autio H, et al. The loop diuretic bumetanide blocks posttraumatic p75NTR upregulation and rescues injured neurons. J Neurosci. 2012 Feb 1;32(5):1757-70. PMID: 22302815.
Dzhala VI, Kuchibhotla KV, Glykys JC, et al. Progressive NKCC1-dependent neuronal chloride accumulation during neonatal seizures. J Neurosci. 2010 Sep 1;30(35):11745-61. PMID: 20810895.
Feig PU. Cellular mechanism of action of loop diuretics: implications for drug effectiveness and adverse effects. Am J Cardiol. 1986 Jan 24;57(2):14A-19A. PMID: 3511652.
