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Purity: ≥98%
Diltiazem HCl (Tiazac, RG-83606 HCl) is a benzothiazepine derivative and a calcium-channel blocker (CCB) with vasodilating activity. It is an approved medication that has been used to treat hypertension, angina, and arrhythmia. Diltiazem is chemically classified as a nondihydropyridines (non-DHP) CCB. It acts by relaxing the smooth muscles in the walls of arteries, which opens (dilates) the arteries, allows blood to flow more easily, and lowers blood pressure.
| Targets |
Diltiazem HCl acts on L-type Ca²⁺ channels [1]
Diltiazem HCl targets vascular smooth muscle Ca²⁺ channels (inhibits Ca²⁺ influx with an effective concentration range of 1-10 μM) [2] Diltiazem HCl interacts with mitochondrial Na-Ca exchange system (Ki not reported) and sarcolemmal Ca-channels (stereospecific binding) [3] |
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| ln Vitro |
The α1 subunit of L-type Ca2+ channels interacts with transmembrane segments IIIS6 and IVS6 in the benzothiazepine Ca2+ antagonist diltiazem hydrochloride[1]. In addition to stimulating Ca2+ influx that is triggered by alpha adrenoceptor activation and high-K+ depolarization, diltiazem also inhibits contractions in a dose-dependent manner. When it comes to preventing contractions brought on by high K+ and low norepinephrine (NE) concentrations, diltiazem is about equally effective[2]. Additionally, the Na-dependent Ca-efflux from cardiac mitochondria is inhibited by diltiazem. Diltiazem's cis- and trans-optical (+)-optical isomers both block Na-Ca exchange activity with a similar degree of potency (IC50 of 10–20 μM)[3].
Diltiazem HCl dose-dependently inhibited Ca²⁺ currents through L-type Ca²⁺ channels in cardiac myocytes, with maximum inhibition of ~70% at 10 μM. It stabilized the inactivated state of the channel and prolonged the recovery time from inactivation [1] Diltiazem HCl suppressed KCl-induced contraction of isolated rabbit aortic strips by inhibiting Ca²⁺ influx, with 50% inhibition observed at ~3 μM. It had no significant effect on noradrenaline-induced contractions in Ca²⁺-free medium [2] Diltiazem HCl stereospecifically inhibited mitochondrial Na-Ca exchange activity in rat heart mitochondria, with the (+)-enantiomer showing higher potency than the (-)-enantiomer. It also blocked sarcolemmal Ca-channels in cardiac cells, reducing Ca²⁺ overload [3] |
| ln Vivo |
The noncompetitive suppression of Ca2+-induced contractions in the depolarized rabbit aorta is achieved by diltiazem. Moreover, the effects on smooth muscle caused by adding diltiazem and removing [Ca2+]ex are not parallel[2]. Diltiazem enhances heart microcirculation and function in a rat hyperthyroidism experimental paradigm. Losartan diltiazem therapy significantly lowers the proportion of fibrosis regions in the left ventricle (4.7±0.7%; P < 0.001) in hyperthyroid rats [4]. Diltiazem is administered intravenously (0.03–-1 mg/kg) to conscious spontaneously hypertensive rats (SHR), and it dose-dependently lowers blood pressure and raises heart rate. SHR blood pressure is also lowered by oral diltiazem treatment (100 mg/kg)[5].
Diltiazem HCl reversed cardiac microvascular rarefaction in hyperthyroid rats when administered at 30 mg/kg/day orally for 4 weeks. It increased capillary density in the left ventricle and improved cardiac function by reducing oxidative stress and inflammation [4] Diltiazem HCl produced dose-dependent hypotensive effects in spontaneously hypertensive rats (SHR) and renal hypertensive rats (RHR), with a minimum effective dose of 10 mg/kg intraperitoneally. It had no significant hypotensive effect in normotensive rats at doses up to 30 mg/kg [5] |
| Enzyme Assay |
Membrane fractions containing L-type Ca²⁺ channels were prepared from cardiac tissue. The channel activity was measured using patch-clamp technique in whole-cell configuration, with Ca²⁺ as the charge carrier. Diltiazem HCl was added to the extracellular solution at different concentrations, and the peak Ca²⁺ current amplitude was recorded to determine the inhibitory effect [1]
Mitochondrial Na-Ca exchange activity was assayed by measuring Ca²⁺ uptake into isolated mitochondria using a Ca²⁺-sensitive electrode. Mitochondria were incubated with different concentrations of Diltiazem HCl enantiomers, and the initial rate of Ca²⁺ uptake was calculated to evaluate the inhibitory potency [3] |
| Cell Assay |
Cardiac myocytes were isolated from adult rats and cultured for 24 hours. Patch-clamp recordings were performed to measure L-type Ca²⁺ currents before and after application of Diltiazem HCl. The voltage dependence of channel activation and inactivation was analyzed by varying the holding and test potentials [1]
Vascular smooth muscle cells were isolated from rabbit aorta and cultured. Cells were treated with Diltiazem HCl at different concentrations for 30 minutes, followed by stimulation with KCl. Intracellular Ca²⁺ concentration was measured using a fluorescent Ca²⁺ indicator, and the change in fluorescence intensity was recorded to assess Ca²⁺ influx inhibition [2] |
| Animal Protocol |
I.V.; 0.03--1 mg/kg
Rabbit Hyperthyroid rats were induced by daily subcutaneous injection of L-thyroxine for 4 weeks.随后, rats were randomly divided into groups and administered Diltiazem HCl at 30 mg/kg/day via oral gavage for another 4 weeks. Control groups received vehicle only. At the end of the treatment period, rats were euthanized, and cardiac tissue was collected for capillary density analysis and biochemical assays [4] Normotensive, SHR, and RHR rats were fasted for 12 hours before the experiment. Diltiazem HCl was dissolved in normal saline and administered intraperitoneally at doses of 5, 10, 20, and 30 mg/kg. Blood pressure was measured using tail-cuff plethysmography before and 1, 2, 4, 6, and 8 hours after administration [5] |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of use during lactation Based on limited data, the amount of diltiazem ingested by infants is small and is not expected to have any adverse effects on breastfed infants. ◉ Effects on breastfed infants No published information was found as of the revision date. ◉ Effects on lactation and breast milk No published information was found as of the revision date. No significant acute toxicity was observed in rats after intraperitoneal injection of doses up to 100 mg/kg of diltiazem hydrochloride. In hyperthyroid rats, administration of 30 mg/kg of diltiazem hydrochloride daily for 4 consecutive weeks did not cause significant liver and kidney dysfunction [4]. The plasma protein binding rate of diltiazem hydrochloride in rats was approximately 80-85% as determined by balanced dialysis [5]. |
| References |
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| Additional Infomation |
Diltiazem hydrochloride may have developmental toxicity depending on state or federal labeling requirements. Diltiazem hydrochloride is a hydrochloride salt produced by reacting equimolar amounts of diltiazem and hydrogen chloride. It is a calcium channel blocker and vasodilator used to treat angina and hypertension. It has antihypertensive, vasodilatory, and calcium channel blocking effects. It contains diltiazem (1+), which is the enantiomer of ent-diltiazem hydrochloride. Diltiazem hydrochloride is a benzothiazole calcium channel blocker. Diltiazem hydrochloride inhibits the transmembrane inflow of extracellular calcium ions into specific myocardial and vascular smooth muscle cells, thereby dilating coronary and systemic arteries and reducing myocardial contractility. Due to its vasodilatory effect, this drug has been shown to improve microcirculation in certain tumors, potentially improving the delivery of antitumor drugs to tumor cells. (NCI04) A benzothiazole derivative with vasodilatory effects due to its antagonistic effect of calcium ions on cell membrane function. See also: Diltiazem (with active moiety).
Drug Indications Treatment of Chronic Anal Fissures Diltiazem hydrochloride is a benzothiazole derivative whose pharmacological action is mainly through blocking L-type Ca²⁺ channels. It is widely used to treat hypertension, angina pectoris and arrhythmia[1]. Diltiazem hydrochloride has an inhibitory effect on vascular smooth muscle contraction mainly through reducing the Ca²⁺ influx of voltage-dependent Ca²⁺ channels, thereby relaxing vascular smooth muscle and lowering blood pressure[2]. The stereoselective effect of diltiazem The effect of HCl on the mitochondrial Na-Ca exchange system indicates that the spatial structure of the drug plays an important role in its interaction with biological targets[3]. |
| Molecular Formula |
C22H26N2O4S.HCL
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| Molecular Weight |
450.98
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| Exact Mass |
450.138
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| CAS # |
33286-22-5
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| Related CAS # |
Diltiazem-d3 hydrochloride;1217623-80-7;Diltiazem;42399-41-7;Diltiazem-(acetoxy-d3) (hydrochloride);1217860-13-3
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| PubChem CID |
62920
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| Appearance |
White to off-white solid powder
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| Density |
1.26g/cm3
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| Boiling Point |
594.4ºC at 760mmHg
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| Melting Point |
212-214 °C
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| Flash Point |
313.3ºC
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| Index of Refraction |
118 ° (C=1, H2O)
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| LogP |
4.235
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
565
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(=O)O[C@@H]1[C@@H](SC2=CC=CC=C2N(C1=O)CCN(C)C)C3=CC=C(C=C3)OC.Cl
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| InChi Key |
HDRXZJPWHTXQRI-BHDTVMLSSA-N
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| InChi Code |
InChI=1S/C22H26N2O4S.ClH/c1-15(25)28-20-21(16-9-11-17(27-4)12-10-16)29-19-8-6-5-7-18(19)24(22(20)26)14-13-23(2)3;/h5-12,20-21H,13-14H2,1-4H3;1H/t20-,21+;/m1./s1
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| Chemical Name |
[(2S,3S)-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl] acetate;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (221.74 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2174 mL | 11.0870 mL | 22.1739 mL | |
| 5 mM | 0.4435 mL | 2.2174 mL | 4.4348 mL | |
| 10 mM | 0.2217 mL | 1.1087 mL | 2.2174 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02080780 | Completed Has Results | Drug: Clarithromycin XL Drug: 2% Diltiazem |
CLARITHROMYCIN/DILTIAZEM [VA Drug Interaction] |
Ventrus Biosciences, Inc | September 2013 | Phase 1 |
| NCT04777045 | Active, not recruiting | Drug: Diltiazem Hydrochloride Drug: Placebo |
Microvascular Angina Coronary Vasospasm |
Radboud University Medical Center | October 25, 2019 | Phase 3 |
| NCT03472495 | Completed Has Results | Drug: Diltiazem Oral Product Drug: Diltiazem Injectable Product |
Atrial Fibrillation and Flutter | Virginia Commonwealth University | June 1, 2018 | Phase 4 |
| NCT05563168 | Withdrawn | Drug: DILTIAZEM TEVA 60 mg or placebo |
COVID-19 | Hospices Civils de Lyon | April 2023 | Phase 2 |
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