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]
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.
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]
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]
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]
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]
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]
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]
^ abcKöppel 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. PMID2176700.
^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. doi:10.1093/oxfordjournals.eurheartj.a061633. PMID6723689.
^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. PMID10944783.
^ abLangenfeld 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. PMID1279606. S2CID25864256.
^ abcdefSowton 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. doi:10.1007/bf00630278. PMID6723753. S2CID20512025.
^ abcdHandler 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. doi:10.1007/bf00544352. PMID4029242. S2CID521671.
^ abMalek 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. PMID15777766. S2CID29226181.
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