Nitrendipine

Nitrendipine
Clinical data
Trade names	Baypress
AHFS/Drugs.com	International Drug Names
Routes of; administration	By mouth
ATC code	C08CA08 ( WHO );
Pharmacokinetic data
Bioavailability	60–70%
Protein binding	98%
Metabolism	Hepatic (completely)
Onset of action	1–2 hours
Elimination half-life	8–24 hours
Excretion	Urine (30%)
Identifiers
	IUPAC name (RS)-3-Ethyl 5-methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate;
CAS Number	39562-70-4 ;
PubChem CID	4507 ;
IUPHAR/BPS	2334 ;
DrugBank	DB01054 ;
ChemSpider	4351 ;
UNII	9B627AW319 ;
KEGG	D00629 ;
ChEBI	CHEBI:7582 ;
ChEMBL	ChEMBL475534 ;
CompTox Dashboard (EPA)	DTXSID0023373 ;
ECHA InfoCard	100.049.540
Chemical and physical data
Formula	C18H20N2O6
Molar mass	360.366 g·mol−1
3D model (JSmol)	Interactive image ;
Chirality	Racemic mixture
Melting point	158 °C (316 °F)
	SMILES O=C(OCC)\C1=C(\N/C(=C(/C(=O)OC)C1c2cccc([N+]([O-])=O)c2)C)C;
	InChI InChI=1S/C18H20N2O6/c1-5-26-18(22)15-11(3)19-10(2)14(17(21)25-4)16(15)12-7-6-8-13(9-12)20(23)24/h6-9,16,19H,5H2,1-4H3 ; Key:PVHUJELLJLJGLN-UHFFFAOYSA-N ;
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Last updated September 30, 2024

Nitrendipine is a dihydropyridine calcium channel blocker. It is used in the treatment of primary (essential) hypertension to decrease blood pressure and can reduce the cardiotoxicity of cocaine.^[1]

Medical uses

Nitrendipine is given to hypertensive individuals in 20 mg oral tablets every day.^[3] This amount is effective in reducing blood pressure by 15–20% within 1–2 hours of administration.^[3] With long-term treatments, the dosage may rise to as much as 40 mg/day; in elderly individuals, a lower dosage of up to 5 mg/day may be equally effective (this reduction in drug amount is attributed to decreased liver function or “first pass” metabolism).^[3] Once digested, nitrendipine is absorbed into the blood and binds to plasma proteins. The majority (98%) is bound to plasma proteins and 70-80% of its inactive polar metabolites are also bound to plasma proteins.^[3] Following hepatic metabolism, 80% of the 20 mg dose can be recovered in the first 96 hours as inactive polar metabolites. The specific volume of distribution of the drug is 2-6 L/kg. In terms of drug half-life, nitrendipine has a half-life of 12–24 hours.^[3] The reported side effects include: headache, flushing, edema and palpitations. These side effects can all be attributed to the vasodilation effect of this drug.^[3]

Mechanism of action

Once nitrendipine is ingested, it is absorbed by the gut and metabolized by the liver before it goes into the systemic circulation and reaches the cells of the smooth muscles and cardiac muscle cells. It binds more effectively with L-type calcium channels in smooth muscle cells because of its lower resting membrane potential.^[4] The nitrendipine diffuses into the membrane and binds to its high affinity binding site on the inactivated L-type calcium channel that's located in between each of the 4 intermembrane components of the α1 subunit.^[4] The exact mechanism of action of nitrendipine is unknown, but it is believed to have important tyrosine and threonine residues in its binding pocket and its binding interferes with the voltage sensor and gating mechanism of the channel.^[4] Thought to have a domain-interface model of binding. In hypertension, the binding of nitrendipine causes a decrease in the probability of open L-type calcium channels and reduces the influx of calcium. The reduced levels of calcium prevent smooth muscle contraction within these muscle cells. Prevention of muscle contraction enables smooth muscle dilation. Dilation of the vasculature reduces total peripheral resistance, which decreases the workload on the heart and prevents scarring of the heart or heart failure.

Nitrendipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid.^[5]

Stereochemistry

Nitrendipine contains a stereocenter and can exist as either of two enantiomers. The pharmaceutical drug is a racemate, an equal mixture of (R)- and the (S)-forms.^[6]

Enantiomers of Nitrendipine
(R)-(+)-Nitrendipine CAS number: 80890-07-9	(S)-(-)-Nitrendipine CAS number: 80873-62-7

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.

Calcium ions (Ca²⁺) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. Many enzymes require calcium ions as a cofactor, including several of the coagulation factors. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.

<span class="mw-page-title-main">Vasodilation</span> Widening of blood vessels

Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel walls are composed of endothelial tissue and a basal membrane lining the lumen of the vessel, concentric smooth muscle layers on top of endothelial tissue, and an adventitia over the smooth muscle layers. Relaxation of the smooth muscle layer allows the blood vessel to dilate, as it is held in a semi-constricted state by sympathetic nervous system activity. Vasodilation is the opposite of vasoconstriction, which is the narrowing of blood vessels.

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

Verapamil, sold under various trade names, is a calcium channel blocker medication used for the treatment of high blood pressure, angina, and supraventricular tachycardia. It may also be used for the prevention of migraines and cluster headaches. It is given by mouth or by injection into a vein.

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> Medication against high blood pressure

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.

Nifedipine, sold under the brand name 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.

Nimodipine, sold under the brand name Nimotop among others, is a calcium channel blocker used in preventing vasospasm secondary to subarachnoid hemorrhage. It was originally developed within the calcium channel blocker class as it was used for the treatment of high blood pressure, but is not used for this indication.

<span class="mw-page-title-main">Methylprednisolone</span> Corticosteroid medication

Methylprednisolone is a synthetic glucocorticoid, primarily prescribed for its anti-inflammatory and immunosuppressive effects. It is either used at low doses for chronic illnesses or used concomitantly at high doses during acute flares. Methylprednisolone and its derivatives can be administered orally or parenterally.

<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">Calciseptine</span> Neurotoxin

Calciseptine (CaS) is a natural neurotoxin isolated from the black mamba Dendroaspis p. polylepis venom. This toxin consists of 60 amino acids with four disulfide bonds. Calciseptine specifically blocks L-type calcium channels, but not other voltage-dependent Ca²⁺ channels such as N-type and T-type channels.

The L-type calcium channel is part of the high-voltage activated family of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. This channel has four isoforms: Cav1.1, Cav1.2, Cav1.3, and Cav1.4.

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.

Barnidipine is a calcium channel blocker which belongs to the dihydropyridine (DHP) group of calcium channel blockers. It is used in the treatment of hypertension.

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">Anipamil</span> Chemical compound

Anipamil is a calcium channel blocker, specifically of the phenylalkylamine type. This type is separate from its more common cousin Dihydropyridine. Anipamil is an analog of the more common drug verapamil, which is the most common type of phenylalkylamine style calcium channel blocker. Anipamil has been shown to be a more effective antiarrhythmic medication than verapamil because it does not cause hypertension as seen in verapamil. It is able to do this by bonding to the myocardium tighter than verapamil.

Macitentan, sold under the brand name Opsumit, is an endothelin receptor antagonist developed by Actelion and approved for the treatment of pulmonary arterial hypertension (PAH). Macitentan is a dual endothelin receptor antagonist, meaning that it acts as an antagonist of two endothelin (ET) receptor subtypes, ET_A and ET_B. However, macitentan has a 50-fold increased selectivity for the ET_A subtype compared to the ET_B subtype.

<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">Lomerizine</span> Chemical compound

Lomerizine (INN) is a diphenylpiperazine class L-type and T-type calcium channel blocker. This drug is currently used clinically for the treatment of migraines, while also being used experimentally for the treatment of glaucoma and optic nerve injury.

References

↑ Trouve R, Nahas G (December 1986). "Nitrendipine: an antidote to cardiac and lethal toxicity of cocaine". Proceedings of the Society for Experimental Biology and Medicine. 183 (3): 392–397. doi:10.3181/00379727-183-3-rc1. PMID 3797422. S2CID 32137604.
↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 464. ISBN 9783527607495.
1 2 3 4 5 6 Siddiqui MA, Plosker GL (2004). "Fixed-dose combination enalapril/nitrendipine: a review of its use in mild-to-moderate hypertension". Drugs. 64 (10): 1135–1148. doi:10.2165/00003495-200464100-00009. PMID 15139792. S2CID 46979688.
1 2 3 Peterson BZ, Tanada TN, Catterall WA (March 1996). "Molecular determinants of high affinity dihydropyridine binding in L-type calcium channels". The Journal of Biological Chemistry. 271 (10): 5293–5296. doi: 10.1074/jbc.271.10.5293 . PMID 8621376.
↑ Luther JM (September 2014). "Is there a new dawn for selective mineralocorticoid receptor antagonism?". Current Opinion in Nephrology and Hypertension. 23 (5): 456–461. doi:10.1097/MNH.0000000000000051. PMC 4248353 . PMID 24992570.
↑ Rote Liste Service GmbH (Hrsg.): Rote Liste 2017 – Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Rote Liste Service GmbH, Frankfurt/Main, 2017, Aufl. 57, ISBN 978-3-946057-10-9, S. 204.

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[1] Trouve R, Nahas G (December 1986). "Nitrendipine: an antidote to cardiac and lethal toxicity of cocaine". Proceedings of the Society for Experimental Biology and Medicine. 183 (3): 392–397. doi:10.3181/00379727-183-3-rc1. PMID 3797422. S2CID 32137604.

[2] Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 464. ISBN 9783527607495.

[Asif-3] 1 2 3 4 5 6 Siddiqui MA, Plosker GL (2004). "Fixed-dose combination enalapril/nitrendipine: a review of its use in mild-to-moderate hypertension". Drugs. 64 (10): 1135–1148. doi:10.2165/00003495-200464100-00009. PMID 15139792. S2CID 46979688.

[Peterson-4] 1 2 3 Peterson BZ, Tanada TN, Catterall WA (March 1996). "Molecular determinants of high affinity dihydropyridine binding in L-type calcium channels". The Journal of Biological Chemistry. 271 (10): 5293–5296. doi: 10.1074/jbc.271.10.5293 . PMID 8621376.

[Luther2014-5] Luther JM (September 2014). "Is there a new dawn for selective mineralocorticoid receptor antagonism?". Current Opinion in Nephrology and Hypertension. 23 (5): 456–461. doi:10.1097/MNH.0000000000000051. PMC 4248353 . PMID 24992570.

[Rote_Liste-6] Rote Liste Service GmbH (Hrsg.): Rote Liste 2017 – Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Rote Liste Service GmbH, Frankfurt/Main, 2017, Aufl. 57, ISBN 978-3-946057-10-9, S. 204.

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