Diltiazem

Diltiazem (200 碌M) elicits a use-dependent blockade that proceeded within a relatively small number of pulses^[1].
Diltiazem reduces Ca²⁺ influx by accelerating inactivation during action potentials, and that the use-dependent blockade is due to increases in the number of channels in a sustained closed state^[1].

Diltiazem (100 mg/kg; p.o.; for 4 weeks) prevents aortic aneurysm formation in a blood pressure-independent manner^[3].
Diltiazem limits aortic aneurysm formation in mice by a blood pressure-independent anti-inflammatory effect on monocytic cells^[3].
Diltiazem (2 mg/kg; i.v.) exhibits T_1/2 of 61.2 min, CL_el of 3.2 mL/min in rats^[4].

[1]. Yoshinari Niimi, et al. Diltiazem facilitates inactivation of single L-type calcium channels in guinea pig ventricular myocytes. Jpn Heart J. 2003 Nov;44(6):1005-14. 

[2]. S Lin Tang, et l. Structural Basis for Diltiazem Block of a Voltage-Gated Ca2+ Channel. Mol Pharmacol. 2019 Oct; 96(4): 485-492. 

[3]. Anja Mieth , et al. L-type calcium channel inhibitor diltiazem prevents aneurysm formation by blood pressure-independent anti-inflammatory effects. Hypertension. 2013 Dec;62(6):1098-104. 

[4]. S. J. Downing, et al. Diltiazem pharmacokinetics in the rat and relationship between its serum concentration and uterine and cardiovascular effects. Br J Pharmacol. 1987 Aug; 91(4): 735-745.