Investigational Drug Details
| Drug ID: | D330 |
| Drug Name: | Nifedipine |
| Synonyms: | |
| Type: | small molecule |
| DrugBank ID: | DB01115 |
| DrugBank Description: | Nifedipine has been formulated as both a long- and short-acting 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, nifedipine prevents calcium-dependent myocyte contraction and vasoconstriction. A second proposed mechanism for the drug’s vasodilatory effects involves pH-dependent inhibition of calcium influx via inhibition of smooth muscle carbonic anhydrase. Nifedipine is used to treat hypertension and chronic stable angina. |
| PubChem ID: | 4485 |
| CasNo: | 21829-25-4 |
| Repositioning for NAFLD: | Yes |
| SMILES: | COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC=C1[N+]([O-])=O)C(=O)OC |
| Structure: |
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| InChiKey: | HYIMSNHJOBLJNT-UHFFFAOYSA-N |
| Molecular Weight: | 346.3346 |
| DrugBank Targets: | Voltage-dependent L-type calcium channel subunit alpha-1C; Voltage-dependent L-type calcium channel subunit alpha-1D; Voltage-dependent L-type calcium channel subunit beta-2; Nuclear receptor subfamily 1 group I member 2; Calmodulin; Voltage-dependent L-type calcium channel subunit alpha-1S; Potassium voltage-gated channel subfamily D member 3; Voltage-dependent T-type calcium channel |
| DrugBank MoA: | Nifedipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload. The vasodilatory effects of nifedipine result in an overall decrease in blood pressure. |
| DrugBank Pharmacology: | Nifedipine, the prototype of the dihydropyridine class of calcium channel blockers (CCBs), is similar to other dihydropyridines including amlodipine, felodipine, isradipine, and nicardipine. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, nifedipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives nifedipine additional arterial selectivity. At therapeutic sub-toxic concentrations, nifedipine has little effect on cardiac myocytes and conduction cells. By blocking the calcium channels, Nifedipine inhibits the spasm of the coronary artery and dilates the systemic arteries, results in a increase of myocardial oxygen supply and a decrease in systemic blood pressure. |
| DrugBank Indication: | For the management of vasospastic angina, chronic stable angina, hypertension, and Raynaud's phenomenon. May be used as a first line agent for left ventricular hypertrophy and isolated systolic hypertension (long-acting agents). |
| Targets: | |
| Therapeutic Category: | |
| Clinical Trial Progress: | |
| Latest Progress: |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0313 | NCT00843349 | COMPLETED | YES | 2009-07 | 2013-06-07 | Details | |
| L0653 | NCT05719376 | PHASE4 | NOT_YET_RECRUITING | NO | 2023-02 | 2023-02-09 | Details |
| L1364 | NCT00250536 | COMPLETED | NO | 2000-03 | 2010-01-14 | Details | |
| L2029 | NCT01545791 | COMPLETED | NO | 2006-05 | 2016-10-28 | Details | |
| L2869 | NCT02735044 | PHASE3 | COMPLETED | YES | 2016-04-14 | 2022-03-25 | Details |
| L3677 | NCT02057172 | PHASE2 | COMPLETED | NO | 2014-01 | 2016-08-09 | Details |
| L4169 | NCT04754334 | PHASE3 | TERMINATED | NO | 2021-03-16 | 2023-02-09 | Details |
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