Cilnidipine

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Cilnidipine
Cilnidipine.svg
Clinical data
Trade names Atelec (アテレック), Cilaheart, Cilacar
AHFS/Drugs.com International Drug Names
ATC code
Identifiers
  • 3-(E)-3-Phenyl-2-propenyl 5-2-methoxyethyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard 100.162.338 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C27H28N2O7
Molar mass 492.528 g·mol−1
3D model (JSmol)
  • O=C(OCCOC)\C2=C(\N/C(=C(/C(=O)OC\C=C\c1ccccc1)C2c3cccc([N+]([O-])=O)c3)C)C

Cilnidipine is a calcium channel blocker. Cilnidipine is approved for use in Japan, China, India, Nepal, and Korea for hypertension.

Contents

It is a calcium antagonist accompanied with L-type and N-type calcium channel blocking functions. Unlike other calcium antagonists, cilnidipine can act on the N-type calcium channel in addition to acting on the L-type calcium channel.

It was patented in 1984 and approved for medical use in 1995. Cilnidipine is currently being repurposed and developed for use in patients with Raynaud's Phenomenon and Systemic Sclerosis by Aisa Pharma, a US biopharma development company. [1]

Medical uses

Cilnidipine decreases blood pressure and is used to treat hypertension and its comorbidities. Due to its blocking action at the N-type and L-type calcium channel, cilnidipine dilates both arterioles and venules, reducing the pressure in the capillary bed. Cilnidipine is vasoselective and has a weak direct dromotropic effect, a strong vasodepressor effect, and an arrhythmia-inhibiting effect. Blood pressure control with cilnidipine treatment in Japanese post-stroke hypertensive patients [The CA-ATTEND study] - the results of a large-scale prospective post-marketing surveillance study of post-stroke hypertensive patients (n = 2667, male 60.4%, 69.0 ± 10.9 years) treated with cilnidipine indicate that cilnidipine was effective in treating uncontrolled blood pressure and was well tolerated in post-stroke hypertensive patients. [2] The Ambulatory Blood Pressure Control and Home Blood Pressure (Morning and Evening) Lowering By N-Channel Blocker Cilnidipine (ACHIEVE-ONE) trial is a large-scale (n=2319) clinical study on blood pressure (BP) and pulse rate (PR) in the real world with use of cilnidipine - this study revealed that Cilnidipine significantly reduced BP and PR in hypertensive patients at the clinic and at home, especially with higher BP and PR in the morning. Cilnidipine is currently being studied in the RECONNOITER study in Australia for its effect on Raynaud's and other manifestations of disease in patients with Systemic Sclerosis. [3] [4]

Side effects

The side effects could be severe dizziness, fast heartbeat, and swelling of face, lips, tongue, eyelids, hands and feet. Lesser side effects include stomach pain, diarrhea and hypotension.

Peripheral edema, a common side effect from the use of amlodipine, was reduced when patients were shifted to cilnidipine. [5]

Brand Name

In India, it is sold under the brand name Cinod, cilacar, clinblue, among others at doses of 5mg/10mg/20mg. [6]

History

It was jointly developed by Fuji Viscera Pharmaceutical Company and Ajinomoto, and was approved to enter the market and be used as an anti-hypertensive in 1995.[ citation needed ]

Related Research Articles

Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as medications to decrease blood pressure in patients with hypertension. CCBs are particularly effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients. Calcium channel blockers are also frequently used to alter heart rate, to prevent peripheral and cerebral vasospasm, and to reduce chest pain caused by angina pectoris.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Amlodipine</span> Dihydropyridine calcium channel blocker used to treat cardiovascular diseases

Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat high blood pressure, coronary artery disease (CAD) and variant angina. It is taken orally.

<span class="mw-page-title-main">Nifedipine</span> Calcium channel blocker medication

Nifedipine, sold under the brand names Adalat and Procardia among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Raynaud's phenomenon, and premature labor. It is one of the treatments of choice for Prinzmetal angina. It may be used to treat severe high blood pressure in pregnancy. Its use in preterm labor may allow more time for steroids to improve the baby's lung function and provide time for transfer of the mother to a well qualified medical facility before delivery. It is a calcium channel blocker of the dihydropyridine type. Nifedipine is taken by mouth and comes in fast- and slow-release formulations.

<span class="mw-page-title-main">Indapamide</span> Thiazide diuretic drug

Indapamide is a thiazide-like diuretic drug used in the treatment of hypertension, as well as decompensated heart failure. Combination preparations with perindopril are available. The thiazide-like diuretics reduce risk of major cardiovascular events and heart failure in hypertensive patients compared with hydrochlorothiazide with a comparable incidence of adverse events. Both thiazide diuretics and thiazide-like diuretics are effective in reducing risk of stroke. Both drug classes appear to have comparable rates of adverse effects as other antihypertensives such as angiotensin II receptor blockers and dihydropyridine calcium channel blockers and lesser prevalence of side-effects when compared to ACE-inhibitors and non-dihydropyridine calcium channel blockers.

<span class="mw-page-title-main">Angiotensin II receptor blocker</span> Group of pharmaceuticals that modulate the renin–angiotensin system

Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system.

<span class="mw-page-title-main">White coat hypertension</span> Medical condition

White coat hypertension (WHT), more commonly known as white coat syndrome, is a form of labile hypertension in which people exhibit a blood pressure level above the normal range in a clinical setting, although they do not exhibit it in other settings. It is believed that the phenomenon is due to anxiety experienced during a clinic visit.

<span class="mw-page-title-main">Moxonidine</span> Chemical compound

Moxonidine (INN) is a new-generation alpha-2/imidazoline receptor agonist antihypertensive drug licensed for the treatment of mild to moderate essential hypertension. It may have a role when thiazides, beta-blockers, ACE inhibitors, and calcium channel blockers are not appropriate or have failed to control blood pressure. In addition, it demonstrates favourable effects on parameters of the insulin resistance syndrome, apparently independent of blood pressure reduction. It is also a growth hormone releaser. It is manufactured by Solvay Pharmaceuticals under the brand name Physiotens & Moxon.

<span class="mw-page-title-main">Labetalol</span> Medication used to treat high blood pressure

Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less preferred than a number of other blood pressure medications. It can be given by mouth or by injection into a vein.

<span class="mw-page-title-main">Nebivolol</span> Chemical compound

Nebivolol is a beta blocker used to treat high blood pressure and heart failure. As with other β-blockers, it is generally a less preferred treatment for high blood pressure. It may be used by itself or with other blood pressure medication. It is taken by mouth.

Hypertensive encephalopathy (HE) is general brain dysfunction due to significantly high blood pressure. Symptoms may include headache, vomiting, trouble with balance, and confusion. Onset is generally sudden. Complications can include seizures, posterior reversible encephalopathy syndrome, and bleeding in the back of the eye.

<span class="mw-page-title-main">Lercanidipine</span> Antihypertensive drug of the calcium channel blocker class

Lercanidipine is an antihypertensive drug. It belongs to the dihydropyridine class of calcium channel blockers, which work by relaxing and opening the blood vessels allowing the blood to circulate more freely around the body. This lowers the blood pressure and allows the heart to work more efficiently.

<span class="mw-page-title-main">Isradipine</span> Antihypertensive drug of the calcium channel blocker class

Isradipine is a calcium channel blocker of the dihydropyridine class. It is usually prescribed for the treatment of high blood pressure in order to reduce the risk of stroke and heart attack.

<span class="mw-page-title-main">Ambulatory blood pressure</span>

Ambulatory blood pressure monitoring (ABPM) measures blood pressure at regular intervals. It is believed to be able to reduce the white coat hypertension effect in which a patient's blood pressure is elevated during the examination process due to nervousness and anxiety caused by being in a clinical setting. ABPM can also detect the reverse condition, masked hypertension, where the patient has normal blood pressure during the examination but uncontrolled blood pressure outside the clinical setting, masking a high 24-hour average blood pressure. Out-of-office measurements are highly recommended as an adjunct to office measurements by almost all hypertension organizations.

<span class="mw-page-title-main">Clevidipine</span> Antihypertensive drug of the calcium channel blocker class

Clevidipine is a dihydropyridine calcium channel blocker indicated for the reduction of blood pressure when oral therapy is not feasible or not desirable. Clevidipine is used IV only and practitioners titrate this drug to lower blood pressure. It has a half-life of approximately one minute. It is rapidly inactivated by esterases.

<span class="mw-page-title-main">Efonidipine</span> Antihypertensive drug of the calcium channel blocker class

Efonidipine (INN) is a dihydropyridine calcium channel blocker marketed by Shionogi & Co. of Japan. It was launched in 1995, under the brand name Landel (ランデル). The drug blocks both T-type and L-type calcium channels. Drug Controller General of India (DCGI) has approved the use of efonidipine in India. It is launched under the brand name "Efnocar".

<span class="mw-page-title-main">Alpha blocker</span> Class of pharmacological agents

Alpha-blockers, also known as α-blockers or α-adrenoreceptor antagonists, are a class of pharmacological agents that act as antagonists on α-adrenergic receptors (α-adrenoceptors).

<span class="mw-page-title-main">Levamlodipine</span> Chemical compound

Levamlodipine (INN), also known as levoamlodipine or S-amlodipine is a pharmacologically active enantiomer of amlodipine. Amlodipine belongs to the dihydropyridine group of calcium channel blocker used as an antihypertensive and antianginal agent. It was approved by the U.S. FDA in December 2019 and is currently marketed under the brand name Conjupri.

<span class="mw-page-title-main">Fimasartan</span> Chemical compound

Fimasartan is a non-peptide angiotensin II receptor antagonist (ARB) used for the treatment of hypertension and heart failure. Through oral administration, fimasartan blocks angiotensin II receptor type 1 (AT1 receptors), reducing pro-hypertensive actions of angiotensin II, such as systemic vasoconstriction and water retention by the kidneys. Concurrent administration of fimasartan with diuretic hydrochlorothiazide has shown to be safe in clinical trials. Fimasartan was approved for use in South Korea on September 9, 2010, and is available under the brand name Kanarb through Boryung Pharmaceuticals, who are presently seeking worldwide partnership.

Refractory Hypertension, also known as a refractory hypertensive state, RfHTN, or status angiotensus, is a hypertensive condition which can occur, for no apparent reason, in patients with previously well-managed hypertension. Refractory hypertension is characterized by a blood pressure that remains uncontrolled on maximal or near-maximal therapy, which is the use of ≥5 antihypertensive agents of different classes, including a long-acting thiazide-like diuretic and spironolactone. Patients with refractory hypertension typically exhibit increased sympathetic nervous system activity. The phenotype of refractory hypertension was first proposed in a retrospective analysis of patients referred to the University of Alabama at Birmingham Hypertension Clinic whose blood pressure could not be controlled on any antihypertensive regimen.

References

  1. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 466. ISBN   9783527607495.
  2. Aoki S, Hosomi N, Nezu T, Teshima T, Sugii H, Nagahama S, et al. (2017). "Blood pressure control with cilnidipine treatment in Japanese post-stroke hypertensive patients: The CA-ATTEND study". Clinical and Experimental Hypertension. 39 (3): 225–234. doi: 10.1080/10641963.2016.1235183 . PMID   28448181.
  3. Kario K, Ando S, Kido H, Nariyama J, Takiuchi S, Yagi T, et al. (February 2013). "The effects of the L/N-type calcium channel blocker (cilnidipine) on sympathetic hyperactive morning hypertension: results from ACHIEVE-ONE". Journal of Clinical Hypertension. 15 (2): 133–42. doi:10.1111/jch.12042. PMC   8034443 . PMID   23339732.
  4. "ANZCTR - Registration".
  5. Minami J, Kawano Y, Makino Y, Matsuoka H, Takishita S (December 2000). "Effects of cilnidipine, a novel dihydropyridine calcium antagonist, on autonomic function, ambulatory blood pressure and heart rate in patients with essential hypertension". British Journal of Clinical Pharmacology. 50 (6): 615–20. doi:10.1046/j.1365-2125.2000.00299.x. PMC   2015014 . PMID   11136301.
  6. "Cilacar (Cilnidipine): Uses, Side Effects, Dosage - Medical Dialogues". Medical Dialogues. 3 March 2021. Retrieved 3 March 2021.

Further reading