(S)-Verapamil (Synonyms: (S)-(-)-Verapamil)

(S)-Verapamil ((S)-(-)-Verapamil) is an orally active MRP1 (ABCC1) modulator with a K d value of 113 nM for hamster MRP1. (S)-Verapamil regulates MRP1, promotes MRP1-mediated glutathione efflux and the transport of calcein and leukotriene C4, reverses glutathione-activated MRP1 ATPase activity, and ultimately depletes intracellular glutathione and induces cell death. (S)-Verapamil specifically induces apoptosis in MRP1-overexpressing tumor cells. (S)-Verapamil can be used in research related to cancer, cardiac diseases such as supraventricular arrhythmia, and hypertension ^{[1] [2]}.

In Vivo, (S)-Verapamil is up to 10 times more potent than (R)-verapamil for negative dromotropic effects on atrioventricular nodal conduction in healthy dogs^[2].

In Vitro, (S)-Verapamil (72 h) potently induces cell death in MRP1-transfected BHK-21 cells^[1]. (S)-Verapamil causes strong and rapid depletion of glutathione inside MRP1-transfected BHK-21 cells^[1]. (S)-Verapamil (30 μM; 10 min) effectively inhibits MRP1-mediated calcein transport in MRP1-transfected BHK-21 cells^[1]. (S)-Verapamil (1-256 μM; in the presence of 3 mM GSH), when combined with 3 mM GSH, potently inhibits ATP-dependent LTC4 transport in MRP1-transfected BHK-21 membrane vesicles^[1]. (S)-Verapamil binds tightly to purified MRP1 with a Kd value of 113 nM, and induces significant conformational changes in purified MRP1^[1]. (S)-Verapamil (4 h) slightly stimulates the basal ATPase activity of purified MRP1, and completely reverses the activation of ATPase activity induced by 5 mM GSH^[1].

References:
[1]. Perrotton T, et al. (R)- and (S)-verapamil differentially modulate the multidrug-resistant protein MRP1. J Biol Chem. 2007;282(43):31542-31548.
[2]. Busse D, et al. Cardiovascular effects of (R)- and (S)-verapamil and racemic verapamil in humans: a placebo-controlled study. Eur J Clin Pharmacol. 2006;62(8):613-619.