Prajmaline

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Prajmaline
Prajmaline.svg
Systematic (IUPAC) name
(4α,16R,17R,21α)-4-propylajmalan-4-ium-17,21-diol
Clinical data
Legal status
?
Identifiers
CAS number 35080-11-6 N
ATC code C01BA08
PubChem CID 37042
ChemSpider 16735977 YesY
UNII 75934UD4GJ YesY
Chemical data
Formula C23H33N2O2+
Mol. mass 369.520 g/mol
 N (what is this?)  (verify)

Prajmaline (Neo-gilurythmal)[1] is a class Ia antiarrhythmic agent[2] which has been available since the 1970s.[3] Class Ia drugs increase the time one action potential lasts in the heart.[4] Prajmaline is a semi-synthetic propyl derivative of ajmaline, with a higher bioavailability than its predecessor.[5] It acts to stop arrhythmias of the heart through a frequency-dependent block of cardiac sodium channels.[2]

Mechanism[edit]

Prajmaline causes a resting block in the heart.[6] A resting block is the depression of a person's Vmax after a resting period. This effect is seen more in the atrium than the ventricle.[6] The effects of some Class I antiarrhythmics are only seen in a patient who has a normal heart rate (~1 Hz).[7] This is due to the effect of a phenomenon called reverse use dependence.[7] The higher the heart rate, the less effect Prajmaline will have.

Uses[edit]

The drug Prajmaline has been used to treat a number of cardiac disorders. These include: coronary artery disease,[8][9] angina,[8][9] paroxysmal tachycardia and Wolff–Parkinson–White syndrome.[1] Prajmaline has been indicated in the treatment of certain disorders where other antiarrhythmic drugs were not effective.[1]

Administration[edit]

Prajmaline can be administered orally,[9] parenterally[8] or intravenously.[8] Three days after the last dose, a limited effect has been observed. Therefore it has been suggested that treatment of arrhythmias with Prajmaline must be continuous to see acceptable results.[1]

Pharmacokinetics[edit]

The main metabolites of Prajmaline are: 21-carboxyprajmaline and hydroxyprajmaline. Twenty percent of the drug is excreted in the urine unchanged.

Daily therapeutic dose is 40–80 mg. Distribution half-life is 10 minutes. Plasma protein binding is 60%. Oral bioavailability is 80%. Elimination half-life is 6 hours. Volume of distribution is 4-5 L/kg. [3]

Side Effects[edit]

There are no significant adverse side-effects of Prajmaline when taken alone and with a proper dosage.[1][8][9] Patients who are taking other treatments for their symptoms (e.g. beta blockers and nifedipine) have developed minor transient conduction defects when given Prajmaline.[8]

Overdose[edit]

An overdose of Prajmaline is possible. The range of symptoms seen during a Prajmaline overdose include: no symptoms, nausea/vomiting, bradycardia, tachycardia, hypotension, and death.[3]

Other Potential Uses[edit]

Due to Prajmaline's sodium channel-blocking properties, it has been shown to protect rat white matter from anoxia (82 +/- 15%).[10][11] The concentration used causes little suppression of the preanoxic response.[10][11]

References[edit]

  1. ^ a b c d e Janicki K, Orski J, Kakol J (1995). "[Antiarrhythmic effects of prajmaline (Neo-Gilurythmal) in stable angina pectoris in light of Holter electrocardiographic monitoring]". Przegląd Lekarski (in Polish) 52 (10): 485–491. PMID 8834838. 
  2. ^ a b Weirich J, Antoni H (June 1990). "Differential analysis of the frequency-dependent effects of class 1 antiarrhythmic drugs according to periodical ligand binding: implications for antiarrhythmic and proarrhythmic efficacy". Journal of Cardiovascular Pharmacology 15 (6): 998–1009. PMID 1694924. 
  3. ^ a b c Köppel C, Oberdisse U, Heinemeyer G (1990). "Clinical course and outcome in class IC antiarrhythmic overdose". Clinical Toxicology 28 (4): 433–44. doi:10.3109/15563659009038586. PMID 2176700. 
  4. ^ Milne JR, Hellestrand KJ, Bexton RS, Burnett PJ, Debbas NM, Camm AJ (February 1984). "Class 1 antiarrhythmic drugs--characteristic electrocardiographic differences when assessed by atrial and ventricular pacing". European Heart Journal 5 (2): 99–107. PMID 6723689. 
  5. ^ Hinse C, Stöckigt J (July 2000). "The structure of the ring-opened N beta-propyl-ajmaline (Neo-Gilurytmal) at physiological pH is obviously responsible for its better absorption and bioavailability when compared with ajmaline (Gilurytmal)". Die Pharmazie 55 (7): 531–2. PMID 10944783. 
  6. ^ a b Langenfeld H, Weirich J, Köhler C, Kochsiek K (February 1990). "Comparative analysis of the action of class I antiarrhythmic drugs (lidocaine, quinidine, and prajmaline) in rabbit atrial and ventricular myocardium". Journal of Cardiovascular Pharmacology 15 (2): 338–45. PMID 1689432. 
  7. ^ a b Langenfeld H, Köhler C, Weirich J, Kirstein M, Kochsiek K (November 1992). "Reverse use dependence of antiarrhythmic class Ia, Ib, and Ic: effects of drugs on the action potential duration?". Pacing and Clinical Electrophysiology 15 (11 Pt 2): 2097–102. doi:10.1111/j.1540-8159.1992.tb03028.x. PMID 1279606. 
  8. ^ a b c d e f Sowton E, Sullivan ID, Crick JC (1984). "Acute haemodynamic effects of ajmaline and prajmaline in patients with coronary heart disease". European Journal of Clinical Pharmacology 26 (2): 147–50. PMID 6723753. 
  9. ^ a b c d Handler CE, Kritikos A, Sullivan ID, Charalambakis A, Sowton E (1985). "Effects of oral prajmaline bitartrate on exercise test responses in patients with coronary artery disease". European Journal of Clinical Pharmacology 28 (4): 371–4. PMID 4029242. 
  10. ^ a b Stys PK (May 1995). "Protective effects of antiarrhythmic agents against anoxic injury in CNS white matter". Journal of Cerebral Blood Flow and Metabolism 15 (3): 425–32. doi:10.1038/jcbfm.1995.53. PMID 7714000. 
  11. ^ a b Malek SA, Adorante JS, Stys PK (March 2005). "Differential effects of Na-K-ATPase pump inhibition, chemical anoxia, and glycolytic blockade on membrane potential of rat optic nerve". Brain Research 1037 (1-2): 171–9. doi:10.1016/j.brainres.2005.01.003. PMID 15777766.