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Prajmaline
Clinical data
ATC code	C01BA08 (WHO) ;
Identifiers
	IUPAC name (4α,16R,17R,21α)-4-propylajmalan-4-ium-17,21-diol;
CAS Number	35080-11-6 ;
PubChem CID	37042;
ChemSpider	16735977 ;
UNII	75934UD4GJ;
CompTox Dashboard (EPA)	DTXSID6023494 ;
Chemical and physical data
Formula	C23H33N2O2+
Molar mass	369.529 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O[C@@H]6C4[C@@H]2C[C@]65c1ccccc1N(C)[C@H]5[C@@H]3C[C@H]4[C@H](CC)[C@@H](O)[N+]23CCC;
	InChI InChI=1S/C23H33N2O2/c1-4-10-25-17-11-14(13(5-2)22(25)27)19-18(25)12-23(21(19)26)15-8-6-7-9-16(15)24(3)20(17)23/h6-9,13-14,17-22,26-27H,4-5,10-12H2,1-3H3/q+1/t13-,14-,17-,18-,19?,20-,21+,22+,23+,25?/m0/s1 ; Key:UAUHEPXILIZYCU-UUEXUKNBSA-N ;
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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

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

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

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

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

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

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

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

^ ^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.
^ ^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. doi:10.1097/00005344-199006000-00019. PMID 1694924.
^ ^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.
^ 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. PMID 6723689.
^ 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.
^ ^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. doi:10.1097/00005344-199002000-00023. PMID 1689432.
^ ^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. S2CID 25864256.
^ ^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. doi:10.1007/bf00630278. PMID 6723753. S2CID 20512025.
^ ^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. doi:10.1007/bf00544352. PMID 4029242. S2CID 521671.
^ ^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.
^ ^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. S2CID 29226181.