Prajmaline
{{short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 464212942
| IUPAC_name = (4α,16R,17R,21α)-4-propylajmalan-4-ium-17,21-diol
| image = Prajmaline.svg
| tradename =
| pregnancy_AU =
| pregnancy_US =
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| legal_AU =
| legal_UK =
| legal_US =
| legal_status =
| routes_of_administration =
| bioavailability =
| protein_bound =
| metabolism =
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| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 35080-11-6
| ATC_prefix = C01
| ATC_suffix = BA08
| PubChem = 37042
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 16735977
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 75934UD4GJ
| C=23 | H=33 | N=2 | O=2 | charge = +
| 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
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = UAUHEPXILIZYCU-UUEXUKNBSA-N
}}
Prajmaline (Neo-gilurythmal){{cite journal |vauthors=Janicki K, Orski J, Kakol J |title=[Antiarrhythmic effects of prajmaline (Neo-Gilurythmal) in stable angina pectoris in light of Holter electrocardiographic monitoring] |language=Polish |journal=Przegląd Lekarski |volume=52 |issue=10 |pages=485–491 |year=1995 |pmid=8834838}} is a class Ia antiarrhythmic agent{{cite journal |vauthors=Weirich J, Antoni H |title=Differential analysis of the frequency-dependent effects of class 1 antiarrhythmic drugs according to periodical ligand binding: implications for antiarrhythmic and proarrhythmic efficacy |journal=Journal of Cardiovascular Pharmacology |volume=15 |issue=6 |pages=998–1009 | date=June 1990 |pmid=1694924 |doi=10.1097/00005344-199006000-00019|doi-access=free }} which has been available since the 1970s.{{cite journal |vauthors=Köppel C, Oberdisse U, Heinemeyer G |title=Clinical course and outcome in class IC antiarrhythmic overdose |journal=Clinical Toxicology |volume=28 |issue=4 |pages=433–44 |year=1990 |pmid=2176700 |doi=10.3109/15563659009038586}} Class Ia drugs increase the time one action potential lasts in the heart.{{cite journal |vauthors=Milne JR, Hellestrand KJ, Bexton RS, Burnett PJ, Debbas NM, Camm AJ |title=Class 1 antiarrhythmic drugs--characteristic electrocardiographic differences when assessed by atrial and ventricular pacing |journal=European Heart Journal |volume=5 |issue=2 |pages=99–107 | date=February 1984 |pmid=6723689 |doi=10.1093/oxfordjournals.eurheartj.a061633}} Prajmaline is a semi-synthetic propyl derivative of ajmaline, with a higher bioavailability than its predecessor.{{cite journal |vauthors=Hinse C, Stöckigt J |title=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) |journal=Die Pharmazie |volume=55 |issue=7 |pages=531–2 | date=July 2000 |pmid=10944783}} It acts to stop arrhythmias of the heart through a frequency-dependent block of cardiac sodium channels.
Mechanism
Prajmaline causes a resting block in the heart.{{cite journal |vauthors=Langenfeld H, Weirich J, Köhler C, Kochsiek K |title=Comparative analysis of the action of class I antiarrhythmic drugs (lidocaine, quinidine, and prajmaline) in rabbit atrial and ventricular myocardium |journal=Journal of Cardiovascular Pharmacology |volume=15 |issue=2 |pages=338–45 | date=February 1990 |pmid=1689432 |doi=10.1097/00005344-199002000-00023|doi-access=free }} 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. The effects of some Class I antiarrhythmics are only seen in a patient who has a normal heart rate (~1 Hz).{{cite journal |vauthors=Langenfeld H, Köhler C, Weirich J, Kirstein M, Kochsiek K |title=Reverse use dependence of antiarrhythmic class Ia, Ib, and Ic: effects of drugs on the action potential duration? |journal=Pacing and Clinical Electrophysiology |volume=15 |issue=11 Pt 2 |pages=2097–102 | date=November 1992 |pmid=1279606 |doi=10.1111/j.1540-8159.1992.tb03028.x|s2cid=25864256 }} This is due to the effect of a phenomenon called reverse use dependence. 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,{{cite journal |vauthors=Sowton E, Sullivan ID, Crick JC |title=Acute haemodynamic effects of ajmaline and prajmaline in patients with coronary heart disease |journal=European Journal of Clinical Pharmacology |volume=26 |issue=2 |pages=147–50 |year=1984 |pmid=6723753 |doi=10.1007/bf00630278|s2cid=20512025 }}{{cite journal |vauthors=Handler CE, Kritikos A, Sullivan ID, Charalambakis A, Sowton E |title=Effects of oral prajmaline bitartrate on exercise test responses in patients with coronary artery disease |journal=European Journal of Clinical Pharmacology |volume=28 |issue=4 |pages=371–4 |year=1985 |pmid=4029242 |doi=10.1007/bf00544352|s2cid=521671 }} angina, paroxysmal tachycardia and Wolff–Parkinson–White syndrome. Prajmaline has been indicated in the treatment of certain disorders where other antiarrhythmic drugs were not effective.
Administration
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.
Side Effects
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.
Other Potential Uses
Due to Prajmaline's sodium channel-blocking properties, it has been shown to protect rat white matter from anoxia (82 +/- 15%).{{cite journal |author=Stys PK |title=Protective effects of antiarrhythmic agents against anoxic injury in CNS white matter |journal=Journal of Cerebral Blood Flow and Metabolism |volume=15 |issue=3 |pages=425–32 | date=May 1995 |pmid=7714000 |doi=10.1038/jcbfm.1995.53|doi-access=free }}{{cite journal |vauthors=Malek SA, Adorante JS, Stys PK |title=Differential effects of Na-K-ATPase pump inhibition, chemical anoxia, and glycolytic blockade on membrane potential of rat optic nerve |journal=Brain Research |volume=1037 |issue=1–2 |pages=171–9 | date=March 2005 |pmid=15777766 |doi=10.1016/j.brainres.2005.01.003|s2cid=29226181 }} The concentration used causes little suppression of the preanoxic response.