Lorcainide

Source: Wikipedia, the free encyclopedia.
Lorcainide
Clinical data
ATC code
Pharmacokinetic data
Protein binding78
Elimination half-life14.3 +/-3.7
Identifiers
  • N-(4-chlorophenyl)-N-(1-isopropylpiperidin-4-yl)-2-phenylacetamide
JSmol)
  • Clc3ccc(N(C(=O)Cc1ccccc1)C2CCN(C(C)C)CC2)cc3
  • InChI=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 checkY
  • Key:XHOJAWVAWFHGHL-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Lorcainide (Lorcainide hydrochloride) is a Class 1c

Janssen Pharmaceutica (Belgium) in 1968 under the commercial name Remivox and is designated by code numbers R-15889 or Ro 13-1042/001.[3] It has a half-life of 8.9 +- 2.3 hrs which may be prolonged to 66 hrs in people with cardiac disease.[2]

Arrhythmia

proarrhythmic.[4]

Wolff–Parkinson–White syndrome

Wolff–Parkinson–White syndrome (WPW) is a pre-excitation syndrome in which individuals are predisposed to supraventricular tachyarrhythmias (rapid and irregular heart beats).[6] People with this condition have an extra or accessory atrioventricular conduction pathway that causes re-entry tachycardia.[6] WPW is characterized by a short PR interval (<0.12 second) and a prolonged, slurred QRS complex (>0.12 seconds).[6]

Class 1c activity

Fast-acting voltage-gated sodium channels (

ECG.[8] Lorcainide also increases the ventricular fibrillation threshold in a dose-dependent fashion.[8] Overall, Lorcainide causes a decrease in tachycardiac events, but also reduced ventricular contractility ejection fraction
. The effect on
sinus node 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.[8]

Other activities

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.[9]

Benefits and risks

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 efficacy.[4] Hematologic, biochemical and urinary analysis of Lorcainide revealed no significant abnormalities.[2] 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.[8] It has a half life of 26.5 +-7.2 hrs.[2]

Synthesis

Lorcainide synthesis:[10][11]

Synthesis starts by reducing the

isopropyl bromide
completes the synthesis of lorcainide (3).

References

  1. S2CID 34275686
    .
  2. ^
    PMID 6198895
    .
  3. doi:10.1111/j.1527-3466.1983.tb00445.x
    .
  4. ^
    ISBN 978-0-07-160405-5
    .
  5. ^
    ISBN 0-7216-0240-1
    .
  6. ^
    PMID 10467188
    .
  7. PMID 8541846
    .
  8. ^
    PMID 6861314
    .
  9. PMID 1667285
    .
  10. ^ DE 2642856, Sanczuk S, Hermans H, "N-Aryl-N-(4-piperidinyl)-arylacetamide, verfahren zu ihrer herstellung und arzneimittel", published 24 March 1977, assigned to Janssen Pharmaceutica NV 
  11. ^ US 4126689, Sanczuk S, Hermans H, "N-aryl-N-(1-alkyl-4-piperidinyl)-arylacetamides", issued 1978, assigned to Janssen Pharmaceutica NV 
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