Repositioning Candidate Details
| Candidate ID: | R1252 |
| Source ID: | DB09227 |
| Source Type: | experimental |
| Compound Type: | small molecule |
| Compound Name: | Barnidipine |
| Synonyms: | Barnidipine; Mepirodipine |
| Molecular Formula: | C27H29N3O6 |
| SMILES: | COC(=O)C1=C(C)NC(C)=C([C@H]1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)O[C@H]1CCN(CC2=CC=CC=C2)C1 |
| Structure: |
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| DrugBank Description: | Barnidipine is a long-acting novel calcium antagonist that belongs to the dihydropyridine (DHP) group of calcium channel blockers. Used in the treatment of hypertension, barnidipine displays high affinity for the calcium channels of the smooth muscle cells in the vascular wall and selectivity against cardiovascular L-type calcium channels . Barnidipine contains two chiral centres thus can have four possible enantiomers. The active component is composed of a single optical isomer (*3'S, 4S* configuration), which is the most potent and longest-acting of the four enantiomers . Compared to several other calcium antagonists which are racemates, the barnidipine compound consisting of a single enantiomer may offer a high degree of pharmacological selectivity . According to a dose-ranging, multicentre, placebo-controlled, double-blind study in patients with mild to moderate hypertension, the antihypertensive response from barnidipine treatment was maintained after a 1-year and 2-year follow-up period in 91% of the patients who had an initial response to the drug . In two European multicentre randomized, double-blind trials, barnidipine was shown to possess equivalent antihypertensive efficacy to amlodipine and nitrendipine, but produced fewer class-specific side-effects . It also demonstrated clinical efficacy which is similar to that of atenolol, enalapril and hydrochlorothiazide . It is available in modified-release oral tablets under the brand name Vasexten to be taken once daily in the morning. Barnidipine has a gradual onset of action and is shown to be well tolerated in patients. It does not produce reflex tachycardia . |
| CAS Number: | 104713-75-9 |
| Molecular Weight: | 491.544 |
| DrugBank Indication: | Indicated for the treatment of mild to moderate essential hypertension and management of chronic stable angina. |
| DrugBank Pharmacology: | Barnidipine reduces peripheral resistance and lowers blood pressure. The chronic use of the drug is not reported to lead to an increase in basic heart frequency. The antihypertensive effects of barnidipine are reported to remain during the entire 24-hour dose interval. Barnidipine does not exert any negative effect on serum lipids profile, glucose level or blood electrolytes . |
| DrugBank MoA: | Barnidipine is a lipophilic 1,4-dihydropyridine calcium antagonist that is characterized by a slow onset of action and a strong and long-lasting binding to the L-type calcium channels . It displays high affinity for the channels expressed in the smooth muscle cells in the vascular wall. Its main mechanism of action arises from the reduction of peripheral vascular resistance secondary to its vasodilatory actions. Calcium ion influx via L-subtype ‘voltage-operated’ channels in the excitable membranes of the smooth muscle cells promotes the formation of calcium-dependent formation of cross-bridges between myosin and actin which are the two major contractile proteins that drive contraction. By blocking the L-type 'voltage-dependent' calcium channels, barnidipine selectively blocks the calcium ion influx in the smooth muscle cells and inhibits the activation of contractile proteins . It is suggested that barnidipine displays a high affinity to the inactivated state of the channel . Like other dihydropyridine calcium antagonists, barnidipine is predicted to interact with the alpha 1-C subunit of the L-type calcium channels. Alpha 1-C subunit of the channel is predicted to reside within the bilayer or channel pore at a location closer to the extracellular rather than the intracellular face of the membrane . Its lipophilicity is likely a reason why barnidipine displays a slow onset and long duration of action. Being a highly lipophilic molecule with an octanol/water partition coefficient of 2000, barnidipine is expected to accumulate in the cell membrane and consequently, gains access to its target receptor in a slow manner . |
| Targets: | Voltage-dependent L-type calcium channel subunit alpha-1C antagonist |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |