U-92032, a T-type Ca2+ channel blocker and antioxidant, reduces neuronal ischemic injuries

Actions of U-92032, a T-Type Ca2+ Channel Antagonist, Support a Functional Linkage Between I T and Slow Intrathalamic Rhythms

“…These and other findings have led to some controversy regarding the T-channel-dependent hypothesis of intrathalamic rhythmicity (reviewed in Crunelli and Leresche 2002;Huguenard 2002). U-92032, (7-[[4-[bis(4-fluorophenyl)methyl]-1-piperazinyl]-methyl]-2-[(2-hydroxyethyl)amino]4-(1-methylethyl)-2,4,6-cycloheptatrien-1-one), has been shown to block I T in guinea pig atrial cells (Xu and Lee 1994), mouse neuroblastoma cells (Ito et al 1994), and isolated hippocampal CA1 pyramidal neurons (Avery and Johnston 1997). While the Ca 2ϩ -current antagonism ascribed to U-92032 is specific for I T compared with higher threshold currents at low concentrations (Ͻ10 M), there is evidence for a significant effect on voltage dependent Na ϩ channels, with 33% blockade at 1 M (Avery and Johnston 1997).…”

A Calcium Antagonist Protects against Doxorubicin-Induced Impairment of Calcium Handling in Neonatal Rat Cardiac Myocytes

“…[15][16][17] Other reports have shown that calcium antagonists effectively inhibit anthracycline-mediated lipid peroxidation. 18,19 Furthermore, recent studies on brain and kidney have reported that antiischemic effects of calcium antagonists may be explained by inhibition of lipid peroxidation [20][21][22] and that the lipophilicity of long-acting calcium antagonists can enhance their antioxidant activity. 20,23 Therefore, the effects of calcium antagonists against DOX-induced cardiotoxicity are not yet well evaluated.…”

Drugs Active at T‐type Ca 2+ Channels

“…One well-studied example is the flunarizine analog U-92032 [69] which is three-orders of magnitude more potent at T-Type channels than methylphenylsuccinimide (MPS) [70].…”