Diltiazem hydrochloride  (Synonyms: CRD-401)

Diltiazem hydrochloride is a Ca²⁺ influx inhibitor (slow channel blocker or calcium antagonist).

Benzothiazepine Ca²⁺ antagonist diltiazem hydrochloride interacts with transmembrane segments IIIS6 and IVS6 in the α1 subunit of L-type Ca²⁺ channels^[1]. Diltiazem causes a dose-dependent inhibiton of contractions as well as Ca²⁺ influx stimulated by alpha adrenoceptor activation and high-K⁺ depolarization. Diltiazem is roughly equally potent in inhibiting contractions induced by high-K⁺ and a low concentration of norepinephrine (NE)^[2]. Diltiazem also inhibits the Na-dependent Ca-efflux from heart mitochondria. Both the (+)-optical isomers of the cis- and trans-forms of diltiazem inhibit Na-Ca exchange activity with comparable potency (IC₅₀ of 10-20 μM)^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Diltiazem produces a noncompetitive inhibition of Ca²⁺-induced contractions of depolarized rabbit aorta. Furthermore, there is a lack of parallelism between the smooth muscle effects of removal of [Ca²⁺]ex and of addition of diltiazem^[2]. Diltiazem improves the cardiac microcirculation and function in an experimental model of hyperthyroidism in rats. The treatment of hyperthyroid rats with losartan diltiazem (4.7±0.7%; P < 0.001) significantly reduces the percentage of fibrosis areas in the left ventricle ^[4]. In conscious spontaneously hypertensive rats (SHR), diltiazem dose-dependently decreases the blood pressure and increases the heart rate after intravenous administration (0.03--1 mg/kg). Oral administration of diltiazem (100 mg/kg) also reduces the blood pressure of SHR^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

450.98

C₂₂H₂₇ClN₂O₄S

33286-22-5

Solid

White to off-white

CN(C)CCN1C2=CC=CC=C2S[C@@H](C3=CC=C(OC)C=C3)[C@@H](OC(C)=O)C1=O.Cl

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [1]. Kraus RL, et al. Molecular mechanism of diltiazem interaction with L-type Ca2+ channels. J Biol Chem. 1998 Oct 16;273(42):27205-12.  [Content Brief]

  [2]. van Breemen C, et al. The mechanism of inhibitory action of diltiazem on vascular smooth muscle contractility. J Pharmacol Exp Ther. 1981 Aug;218(2):459-63.  [Content Brief]

  [3]. Chiesi M, et al. Stereospecific action of diltiazem on the mitochondrial Na-Ca exchange system and on sarcolemmal Ca-channels. Biochem Pharmacol. 1987 Sep 1;36(17):2735-40.  [Content Brief]

  [4]. Freitas F, et al. Cardiac microvascular rarefaction in hyperthyroid rats is reversed by losartan, diltiazem, and propranolol. Fundam Clin Pharmacol. 2015 Feb;29(1):31-40.  [Content Brief]

  [5]. Sato M, et al. Hypotensive effects of diltiazem hydrochloride in the normotensive, spontaneously hypertensive and renal hypertensive rats (author's transl). Nihon Yakurigaku Zasshi. 1979 Mar;75(2):99-106.  [Content Brief]