| Revision as of 12:21, 23 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456519725 of page Lorcainide for the Chem/Drugbox validation project (updated: 'CAS_number'). |
Latest revision as of 08:18, 9 September 2024 edit JWBE (talk | contribs)Extended confirmed users10,126 edits removed Category:Chloroarenes; added Category:4-Chlorophenyl compounds using HotCat |
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{{short description|Antiarrythmic agent}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Drugbox |
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{{Drugbox |
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| Verifiedfields = changed |
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| Verifiedfields = changed |
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| verifiedrevid = 408579839 |
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| verifiedrevid = 462093837 |
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| IUPAC_name = ''N''-(4-chlorophenyl)-''N''-(1-isopropylpiperidin-4-yl)-2-phenylacetamide |
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| IUPAC_name = ''N''-(4-chlorophenyl)-''N''-(1-isopropylpiperidin-4-yl)-2-phenylacetamide |
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| image = Lorcainide.svg |
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| image = Lorcainide.svg |
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| legal_US = <!-- OTC / Rx-only --> |
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| legal_US = <!-- OTC / Rx-only --> |
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| legal_status = |
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| legal_status = |
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| routes_of_administration = |
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| routes_of_administration = |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| metabolism = |
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| metabolism = |
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| elimination_half-life = 14.3 +/-3.7 |
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| elimination_half-life = 14.3 +/-3.7 |
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| excretion = |
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| excretion = |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number = <!-- blanked - oldvalue: 59729-31-6 --> |
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| CAS_number = 59729-31-6 |
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| ATC_prefix = C01 |
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| ATC_prefix = C01 |
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| ATC_suffix = BC07 |
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| ATC_suffix = BC07 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 39116 |
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| ChemSpiderID = 39116 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = KGJ2T0N7IQ |
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| UNII = KGJ2T0N7IQ |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=22 | H=27 | Cl=1 | N=2 | O=1 |
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| C=22 | H=27 | Cl=1 | N=2 | O=1 |
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| molecular_weight = 370.915 g/mol |
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| smiles = Clc3ccc(N(C(=O)Cc1ccccc1)C2CCN(C(C)C)CC2)cc3 |
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| smiles = Clc3ccc(N(C(=O)Cc1ccccc1)C2CCN(C(C)C)CC2)cc3 |
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| InChI = 1/C22H27ClN2O/c1-17(2)24-14-12-21(13-15-24)25(20-10-8-19(23)9-11-20)22(26)16-18-6-4-3-5-7-18/h3-11,17,21H,12-16H2,1-2H3 |
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| InChIKey = XHOJAWVAWFHGHL-UHFFFAOYAL |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C22H27ClN2O/c1-17(2)24-14-12-21(13-15-24)25(20-10-8-19(23)9-11-20)22(26)16-18-6-4-3-5-7-18/h3-11,17,21H,12-16H2,1-2H3 |
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| StdInChI = 1S/C22H27ClN2O/c1-17(2)24-14-12-21(13-15-24)25(20-10-8-19(23)9-11-20)22(26)16-18-6-4-3-5-7-18/h3-11,17,21H,12-16H2,1-2H3 |
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| StdInChIKey = XHOJAWVAWFHGHL-UHFFFAOYSA-N |
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| StdInChIKey = XHOJAWVAWFHGHL-UHFFFAOYSA-N |
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}} |
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'''Lorcainide''' (Lorcainide hydrochloride) is a Class 1c ] that is used to help restore normal heart rhythm and conduction in patients with ], ]c<ref name="Samánek_1987" /> and ].<ref name="Winkle_1984" /> Lorcainide was developed by ] (Belgium) in 1968 under the commercial name Remivox and is designated by code numbers R-15889 or Ro 13-1042/001.<ref name = "Amery_1983" /> It has a half-life of 8.9 +- 2.3 hrs which may be prolonged to 66 hrs in people with cardiac disease.<ref name="Winkle_1984" /> |
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==Arrhythmia== |
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] is a heart rate disorder that manifests as an altered cardiac rhythm. It results from either abnormal ] activity or a disturbance in impulse propagation, or both.<ref name = "Katzung_2009" /> Arrhythmias can be caused by various conditions including ], ], pH disruptions, B adrenergic activation, drug interactions or the presence of diseased tissue.<ref name = "Guyton_2006" /> These events can trigger the development of ] in the heart, which emit abnormal impulses at random times during the ]. An arrhythmia can present itself as either ] or ].<ref name = "Guyton_2006" /> Untreated arrhythmias may progress to ] or ].<ref name = "Guyton_2006" /> Treatment is aimed at normalizing cardiac rhythm by altering ion flow across the membrane. ] can reduce arrhythmia related symptoms such as ] or ]; however, they often have a narrow ] and can also be ].<ref name = "Katzung_2009" /> |
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==Wolff–Parkinson–White syndrome== |
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] (WPW) is a ] in which individuals are predisposed to supraventricular tachyarrhythmias (rapid and irregular heart beats).<ref name="Al-Khatib_1999" /> People with this condition have an extra or accessory ] conduction pathway that causes re-entry tachycardia.<ref name="Al-Khatib_1999" /> WPW is characterized by a short ] (<0.12 second) and a prolonged, slurred ] (>0.12 seconds).<ref name="Al-Khatib_1999" /> |
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==Class 1c activity== |
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Fast-acting voltage-gated sodium channels (]) found in high concentrations in the ventricular myocytes, open at a membrane potential of −80 mv in typical cardiac rhythm. This will result in a rapid upstroke of an ] that leads to contraction of the ventricles.<ref name="Wang_1995" /> Class 1c drugs have local ] properties and have a high affinity for open Nav1.5 (but not closed or inactive Nav1.5), thus irreversibly binding and reducing the fast Na+ influx. Interactions of Lorcainide with Nav1.5 are time and voltage dependent. Class 1c drugs have a characteristically slow dissociation rate, which will slow the upstroke duration and amplitude of ventricular myocytes’ action potential and prolong the PR, QRS and QT intervals of an ].<ref name="Echt_1983" /> Lorcainide also increases the ventricular fibrillation threshold in a dose-dependent fashion.<ref name="Echt_1983" /> Overall, Lorcainide causes a decrease in tachycardiac events, but also reduced ventricular contractility ]. |
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The effect on ] function is controversial, as some researchers have noted a decreased sinus cycle length and increase in sinus node recovery, whereas others have observed no change.<ref name="Echt_1983" /> |
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==Other activities== |
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Lorcainide inhibits adenosine 5’-triphosphate (ATP)-hydrolytic action of myocardial Na+K+ATPase in-vitro in a concentration dependent manner. The mode of action and the implications of this finding are not well known.<ref name="Almotrefi_1991" /> |
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==Benefits and risks== |
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Lorcainide exhibits a prolonged duration of action (approximately 8-10 hrs), is well absorbed when taken orally and has a good safety profile as well as a good drug ].<ref name = "Katzung_2009" /> Hematologic, biochemical and urinary analysis of Lorcainide revealed no significant abnormalities.<ref name="Winkle_1984" /> However, an increased prevalence of central nervous system effects, including headache, dizziness and sleep disturbances have been associated with oral dosages of Lorcainide when compared to intravenous administration. This could be due to a greater accumulation of plasma Noriorcainide when exposed to oral Lorcainide. Noriorcainide, an N-dealkylated derivative, is an active metabolite of Lorcainide. It is as potent as its parent compound with similar antiarrhythmic efficacy, wherein it suppresses chronic premature ventricular complexes.<ref name="Echt_1983" /> It has a half life of 26.5 +-7.2 hrs.<ref name="Winkle_1984" /> |
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==Synthesis== |
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:] |
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The starting material is the ] formed by combining ] and ''N''-carbethoxy-4-piperidone, which is ] with ] and then ] with the ] of ] to produce an ]. Selective ] with ], followed by ] with ] gives lorcainide.<ref>{{cite patent | country = US | number = 4126689 | title = N-aryl-N-(1-alkyl-4-piperidinyl)-arylacetamides | inventor = Sanczuk S, Hermans H | assign1 = Janssen Pharmaceutica NV | gdate = 1978 }}</ref><ref>{{cite web |url=https://www.chemdrug.com/article/8/3284/16419861.html |title=Lorcainid |website=chemdrug.com |date=23 November 2018 |access-date=2024-07-01}}</ref> |
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==References== |
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{{Reflist|30em|refs = |
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<ref name="Al-Khatib_1999">{{cite journal | vauthors = Al-Khatib SM, Pritchett EL | title = Clinical features of Wolff-Parkinson-White syndrome | journal = American Heart Journal | volume = 138 | issue = 3 Pt 1 | pages = 403–13 | date = September 1999 | pmid = 10467188 | doi = 10.1016/s0002-8703(99)70140-7 }}</ref> |
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<ref name="Amery_1983">{{cite journal | vauthors = Amery WK, Aerts T | title = Lorcainide | journal = Cardiovascular Drug Reviews | date = March 1983 | volume = 1 | issue = 1 | pages = 109–32 | doi = 10.1111/j.1527-3466.1983.tb00445.x | doi-access = free }}</ref> |
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<ref name="Almotrefi_1991">{{cite journal | vauthors = Almotrefi AA, Dzimiri N | title = Variations in potassium concentration modify the inhibitory effect of lorcainide on myocardial Na(+)-K(+)-ATPase activity | journal = British Journal of Pharmacology | volume = 104 | issue = 4 | pages = 793–6 | date = December 1991 | pmid = 1667285 | pmc = 1908833 | doi = 10.1111/j.1476-5381.1991.tb12508.x }}</ref> |
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<ref name="Echt_1983">{{cite journal | vauthors = Echt DS, Mitchell LB, Kates RE, Winkle RA | title = Comparison of the electrophysiologic effects of intravenous and oral lorcainide in patients with recurrent ventricular tachycardia | journal = Circulation | volume = 68 | issue = 2 | pages = 392–9 | date = August 1983 | pmid = 6861314 | doi = 10.1161/01.cir.68.2.392 | doi-access = free }}</ref> |
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<ref name="Guyton_2006">{{cite book | vauthors = Guyton A, Hall J | date =2006 | title = Textbook of Medical Physiology | edition = 11th | location = Philadelphia | publisher = Elsevier Saunders | isbn = 0-7216-0240-1}}</ref> |
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<ref name="Katzung_2009">{{cite book | vauthors = Katzung B, Masters S, Trevor A | date = 2009 | title = Basic and Clinical Pharmacology | edition = 11th | location = New York | publisher = McGraw Hill | isbn = 978-0-07-160405-5 }}</ref> |
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<ref name="Samánek_1987">{{cite journal | vauthors = Samánek M, Hrobonová V, Bartáková H | title = Lorcainide treatment of Wolff-Parkinson-White syndrome in children and adolescents | journal = Pediatric Cardiology | volume = 8 | issue = 1 | pages = 3–9 | date = 1987 | pmid = 2440013 | doi = 10.1007/BF02308377 | s2cid = 34275686 }}</ref> |
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<ref name="Wang_1995">{{cite journal | vauthors = Wang Q, Shen J, Li Z, Timothy K, Vincent GM, Priori SG, Schwartz PJ, Keating MT | title = Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia | journal = Human Molecular Genetics | volume = 4 | issue = 9 | pages = 1603–7 | date = September 1995 | pmid = 8541846 | doi = 10.1093/hmg/4.9.1603 }}</ref> |
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<ref name="Winkle_1984">{{cite journal | vauthors = Winkle RA, Keefe DL, Rodriguez I, Kates RE | title = Pharmacodynamics of the initiation of antiarrhythmic therapy with lorcainide | journal = The American Journal of Cardiology | volume = 53 | issue = 4 | pages = 544–51 | date = February 1984 | pmid = 6198895 | doi = 10.1016/0002-9149(84)90028-6 }}</ref> |
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{{Antiarrhythmic agents}} |
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