Prajmaline

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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., J. Orski, and J. Kakol. "Antiarrhythmic Effects of Prajmaline (Neo-Gilurythmal) in Stable Angina Pectoris." Przegl Lek 52.10 (1995): 485-91. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/8834838>.
  2. ^ a b Weirich, J., and H. Antoni. "Differential Analysis of the Frequency-Dependent Effects of Class 1 Antiarrhythmic Drugs According to Periodical Ligand Binding." Journal of Cardiovascular Pharmacology 15.6 (1990): 998-1009. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/1694924>.
  3. ^ a b c Koppel, Claus, Ursula Oberdisse, and Gerhard Heinemeyer. "Clinical Course and Outcome in Class IC Antiarrhythmic Overdose." Clinical Toxicology 28.4 (1990): 433-44. Web. 6 Feb. 2011. <http://informahealthcare.com/doi/pdf/10.3109/15563659009038586>.
  4. ^ Milne, J. R., K. J. Hellestrand, R. S. Bexton, P. J. Burnett, N. Debbas, and A. Camm. "Class 1 Antiarrhythmic Drugs — Characteristic Electrocardiographic Differences When Assessed by Atrial and Ventricular Pacing." European Heart Journal 5 (1984): 99-107. Web. 6 Feb. 2011. <http://eurheartj.oxfordjournals.org/content/5/2/99.full.pdf>.
  5. ^ Hinse, C., and J. Stöckigt. "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)." Pharmazie 55.7 (2000): 531-32. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/10944783>.
  6. ^ a b Langenfeld, H., J. Weirich, C. Köhler, and K. Kochsiek. "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 (1990): 338-45. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/1689432>.
  7. ^ a b Langenfeld, H., C. Köhler, J. Weirich, M. Kirstein, and K. Kochsiek. "Reverse Use Dependence of Antiarrhythmic Class Ia, Ib, and Ic: Effects of Drugs on the Action Potential Duration?" Pacing and Clinical Electrophysiology 2nd ser. 15.11 (1992): 2097-102. Web. 6 Feb. 2011. <http://onlinelibrary.wiley.com/doi/10.1111/j.1540-8159.1992.tb03028.x/pdf>.
  8. ^ a b c d e f Sowton, E., I. D. Sullivan, and J. C. P. Crick. "Acute Haemodynamic Effects of Ajmaline and Prajmaline in Patients with Coronary Heart Disease." European Journal of Clinical Pharmacology 26.2 (1984): 147-50. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/6723753>.
  9. ^ a b c d Handler, C. E., A. Kritikos, I. D. Sullivan, A. Charalambakis, and E. Sowton. "Effects of Oral Prajmaline Bitartrate on Exercise Test Responses in Patients with Coronary Artery Disease." European Journal of Clinical Pharmacology 28.4 (1985): 371-74. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/4029242>.
  10. ^ a b Stys, PK. "Protective Effects of Antiarrhythmic Agents against Anoxic Injury in CNS White Matter." Journal of Cerebral Blood Flow & Metabolism 15.3 (1995): 425-32. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/7714000>.
  11. ^ a b Malek, S., J. Adorante, and P. Stys. "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 (2005): 171-79.