{{Short description|Antihypertensive drug of the calcium channel blocker class}} {{Infobox drug | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 408771000 | IUPAC_name = (''RS'')-3-Ethyl 5-methyl 2,6-dimethyl-4-(''m''-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate | image = (RS)-Nitrendipin Structural Formula V1.svg | image_class = skin-invert-image | alt = Skeletal formula of nitrendipine | width = 200 | image2 = Nitrendipine-3D-balls.png | image_class2 = bg-transparent | alt2 = Ball-and-stick model of the nitrendipine molecule | chirality = Racemic mixture <!--Clinical data--> | tradename = Baypress | Drugs.com = {{drugs.com|international|nitrendipine}} | MedlinePlus = | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_category = | legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 --> | legal_UK = <!-- GSL / P / POM / CD --> | legal_US = <!-- OTC / Rx-only --> | legal_status = | routes_of_administration = By mouth <!--Pharmacokinetic data--> | bioavailability = 60–70% | protein_bound = 98% | metabolism = Hepatic (completely) | onset = 1–2 hours | elimination_half-life = 8–24 hours | excretion = Urine (30%) <!--Identifiers--> | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 39562-70-4 | ATC_prefix = C08 | ATC_suffix = CA08 | PubChem = 4507 | IUPHAR_ligand = 2334 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01054 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4351 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 9B627AW319 | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 7582 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00629 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 475534 <!--Chemical data--> | C=18 | H=20 | N=2 | O=6 | smiles = O=C(OCC)\C1=C(\N/C(=C(/C(=O)OC)C1c2cccc([N+]([O-])=O)c2)C)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = PVHUJELLJLJGLN-UHFFFAOYSA-N | melting_point = 158 }} '''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.<ref>{{cite journal | vauthors = Trouve R, Nahas G | title = Nitrendipine: an antidote to cardiac and lethal toxicity of cocaine | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 183 | issue = 3 | pages = 392–397 | date = December 1986 | pmid = 3797422 | doi = 10.3181/00379727-183-3-rc1 | s2cid = 32137604 }}</ref>
<!-- Society and culture --> It was patented in 1971 and approved for medical use in 1985.<ref>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=464 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA464 |language=en}}</ref>
== Medical uses == Nitrendipine is given to hypertensive individuals in 20 mg oral tablets every day.<ref name = "Asif">{{cite journal | vauthors = Siddiqui MA, Plosker GL | title = Fixed-dose combination enalapril/nitrendipine: a review of its use in mild-to-moderate hypertension | journal = Drugs | volume = 64 | issue = 10 | pages = 1135–1148 | year = 2004 | pmid = 15139792 | doi = 10.2165/00003495-200464100-00009 | s2cid = 46979688 }}</ref> This amount is effective in reducing blood pressure by 15–20% within 1–2 hours of administration.<ref name = "Asif" /> 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).<ref name = "Asif" /> 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.<ref name = "Asif" /> 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.<ref name = "Asif" /> The reported side effects include: headache, flushing, edema and palpitations. These side effects can all be attributed to the vasodilation effect of this drug.<ref name = "Asif" />
== 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.<ref name = "Peterson">{{cite journal | vauthors = Peterson BZ, Tanada TN, Catterall WA | title = Molecular determinants of high affinity dihydropyridine binding in L-type calcium channels | journal = The Journal of Biological Chemistry | volume = 271 | issue = 10 | pages = 5293–5296 | date = March 1996 | pmid = 8621376 | doi = 10.1074/jbc.271.10.5293 | doi-access = free }}</ref> The nitrendipine diffuses into the membrane and binds to its high affinity binding site on the inactivated <small>L</small>-type calcium channel that's located in between each of the 4 intermembrane components of the α1 subunit.<ref name = "Peterson" /> 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.<ref name = "Peterson" /> Thought to have a domain-interface model of binding. In hypertension, the binding of nitrendipine causes a decrease in the probability of open <small>L</small>-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.<ref name="Luther2014">{{cite journal | vauthors = Luther JM | title = Is there a new dawn for selective mineralocorticoid receptor antagonism? | journal = Current Opinion in Nephrology and Hypertension | volume = 23 | issue = 5 | pages = 456–461 | date = September 2014 | pmid = 24992570 | pmc = 4248353 | doi = 10.1097/MNH.0000000000000051 }}</ref>
== 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.<ref name="Rote Liste">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.</ref> {| class="wikitable" style="text-align:center" |- class="hintergrundfarbe6" ! colspan="2"| Enantiomers of Nitrendipine |- | 200 px<br />(''R'')-(+)-Nitrendipine<br><small> CAS number: 80890-07-9</small> | 200 px<br />(''S'')-(-)-Nitrendipine<br><small> CAS number: 80873-62-7</small> |}
== References == {{reflist}}
{{Channelergics}} {{Glycinergics}} {{Mineralocorticoidics}}
Category:Antimineralocorticoids Category:Calcium channel blockers Category:Dihydropyridines Category:3-Nitrophenyl compounds Category:Carboxylate esters Category:Glycine receptor antagonists Category:Methyl esters Category:Ethyl esters