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 October 23, 2023

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.

Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations. It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit muscle, the whole bundle or sheet of smooth muscle cells contracts as a syncytium.

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.

Calcium metabolism is the movement and regulation of calcium ions (Ca²⁺) in (via the gut) and out (via the gut and kidneys) of the body, and between body compartments: the blood plasma, the extracellular and intracellular fluids, and bone. Bone acts as a calcium storage center for deposits and withdrawals as needed by the blood via continual bone remodeling.

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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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