Quinidine Ajmaline

I a With prolongation of action potential Quinidine, Procainamide, Disopyramide, Ajmaline, Prajmaline... 

Antiarrhythmics representative of these categories include Class lA— quinidine, procainamide, ajmaline, dis-opyramide, propafenone Class IB—lido-caine, mexiletine, tocainide, as well as phenytoin Qass 1C—flecainide. 

Cardiovascular Acetyldigosin, ajmaline, amiodarone, aprindine, bepridil, bezaflbrate, captopril, dinepazide, clopidogrel, coumarins, diazoxide, digoxin, dipyridamole, disopyramide, doxazosin, enalapril, flurbiprofen, fur-oxemide, hydralazine, lisinopril methyldopa, metolazone, nifedipine, phenindione, procainamide, propanolol, propafenone, quinidine, ramapril, spironolactone, thiazide diuretics, ticlopidine, vesnarinone... 

The increase in heart muscle excitability induced by some natural quinuclidine derivatives (quinidine, ajmaline), suggesting pharmacological activity of some synthetic quinuclidine compounds and the possibility of using quinuclidines as catalysts for production of polymers,17 stimulated further interest in the ring system. 

Mechanism of action. Na -channel blocking antiarrhythmics resemble most local anesthetics in being cationic amphiphilic molecules (p.206 exception phenytoin, p.191). Possible molecular mechanisms of their inhibitory effects are outlined on p.202 in more detail. Their low structural specificity is reflected by a low selectivity toward different cation channels. Besides the Na channel. Carotid 1C channels are also likely to be blocked. Accordingly, cationic amphiphilic antiarrhythmics affect both the depolarization and repolarization phases. Depending on the substance, AP duration can be increased (Class IA), decreased (Class IB), or remain the same (Class IC). Antiarrhythmics representative of these categories include Class IA—quinidine, procainamide, ajmaline, disopyramide Class IB—lidocaine, mexile-tine, tocainide Class IC—flecainide, propafenone. 

Ajmaline has long been known to possess antifibrillatory properties (72), but it does not seem to be superior to quinidine which is used clinically for this purpose, although it is far from an ideal drug. Ajmaline produces no sedation or tranquilization and its blood pressure properties are unremarkable in the various specialized situations in which it has been placed (73). Similar remarks hold for isoajmaline (74). 

Aconitine and related diterpene alkaloids (A) veratridine, zygadenine, and related steroidal alkaloids (A) ajmaline, vincamine, ervatamine, and other indole alkaloids (AA) dicentrine and other aporphine alkaloids (AA) gonyautoxin (AA) paspalitrem and related indoles (AA) phalloidin (AA) quinidine and related quinoline alkaloids (AA) sparteine and related quinolizidine alkaloids (AA) saxitoxin (AA) strychnine (AA) tetrodotoxin (AA)... 

A,codeine,morphine,dihydrocodeine,quinine, quinidine,caffeine, theophylline, ajmaline Various basic drugs Separation of basic drugs on silica gel with non-aqueous ionic eluents Spherisorb S5W Silica 250x4.9 Me0H-hexane(85 15)contai ni ng o.iox hcio4 66 ... 

COIB A Antiarrhythmics Class I The natural products quinidine and ajmaline belong to the group of blocking agents of the so-called rapid sodium channels in the cell membrane. 

AJMALINE The alkaloid ajmaline is isolated from the root of Rauvolfia serpentine and other Rauvolfia species, family Apocynaceae (see section C02, Antihypertensives). Ajmaline has a very similar mode of action to quinidine. It works through retardation of the speed of depolarisation and repolarisation as well as a retardation of the reactivation of the sodium-system. Its sedative effect is weak. 

More interesting is the pharmacology of ajmaline (37), which is available in large quantities as a by-product of the reserpine extraction. Detailed pharmacological studies seemed to be more than justified because reserpine did not possess all the pharmacological effects of crude Rauwolfia extracts. Ajmaline was compared with quinidine and studied clinically in cardiac arrhythmias,... 

Ajmaline, ajamlicine, flecainide, fluoxetine, isoniazid, ketoconazole, lobeline, nefazodone, paroxetine, (7 )-propaphenooe, quinidine, ritonavir, "statins," yohimbine, venlafaxine... 

Alkaloids which modulate ion channels are tabulated in Table 10. Voltagegated Na+ channels are a target for several steroidal alkaloids, (e.g., batrachotoxinin, samandarine, veratrine, veratridine and zygadenine), indole alkaloids (e.g., ajmaline), aporphines (e.g., dicentrine, liriodenine), quinoline alkaloids (quinine, quinidine), quinolizidine alkaloids (e.g., sparteine, lupanine), and furthermore, for alkaloids present in animals or venoms (e.g., chiriquitoxin, i-conotoxins, dibromosceptrine, gonyauxtoxins, histrionicotoxins, pumiliotoxins, saxitoxin and tetrodotoxin). 

Protein biosynthesis is essential for all cells and thus provides another important target. Indeed, a number of alkaloids have been detected (although not too many have been studied in this context) which inhibit protein biosynthesis in vitro. Emetine from Cephaelis ipecacuanha (Rubiaceae) is the most potent plant constituent other alkaloids with the same ability include harringtonine, homoharringtonine, cryptopleurine, tubulosine, hemanthamine, lycorine, narciclasine, pretazettine, pseudolycorine, tylocrepine, and tylopherine [5] and furthermore, ajmaline, berberine, boldine, cinchonine, cinchonidine, harmalin, harmin, lobeline, norharman, papaverine, quinidine, quinine, salsoline, sanguinarine,... 

Ajmaline, berbamine, berberine, boldine, cinchonine, cinchonidine, ergometrine, harmalin, harmin, lobeline, norharman, papaverine, quinidine, quinine, sanguinarine, and solanine affect more than one of the basic... 

Whereas most alkaloids appear to be specifically directed towards animals, others show a broader activity spectrum. For example, alkaloids with marked antibacterial activities include ajmaline, berberine, boldine, cinchonidine, cinchonine, harmaline, harmine, lobeline, narcotine, norharman, quinidine, quinine, sanguinarine, strychnine and yohimbine (see reviews [5, 73, 96]. Only the benzophenanthridine alkaloid... 

Interfering ajmaline, alprazolam, celiprolol, clobazam, cycloguanil, debrisoquine, dextromethorphan, disopyramide, ketamine, lorazepam, mephentermine, methaqualone, metoprolol, minoxidil, nifedipine, nitrazepam, oxazepam, pentazocine, piroxicam, prilocaine, quinidine, quinine, sulindac, tiaprofenic acid, tofisopam, yohimbine, zopiclone... 

Simultaneous N-acetylprocainamide, ajmaline, chlorpromeizine, desipramine, dipyridamole, doxazosin, flecainide, durazepam, gallopamil, imipramine, keteuiserin, metoprolol, mexiletine, mianserin, nadolol, nitrazepam, orphenadrine, oxprenolol, penbutolol, pindolol, prqjmalium, procainamide, propranolol, protriptyline, p3Timethamine, quinidine, quinine, triamterene, trimipramine, verapamil... 

Additional evidence for an antifibrillatory action for ajmaline was supplied by van Dongen (13). He found that in the decerebrate cat 0.5 mg./kg. ajmaline increased the amount of faradic current required to produce auricular fibrillation, ventricular fibrillation, and post-stimulus arrhythmias. This action differs from that of quinidine, which prolonged auricular conduction time and atrioventricular conduction times by 52-100 %, while ajmaline did not alter refractory periods or conduction times. Heterotropic cardiac rhythms were produced by a variety of means (barium chloride, epinephrine, and strophantin-ephedrine) which in all cases may be prevented by ajmaline. 

OATP1A2 (OATP-A) Ajmalin, DHEA-Sulfate, 17(1-Estradiol, Estrone, Microcystin, N-Methyl-quinidine, Ouabain, Prostaglandin E2, Rocuronium, Thyroxin (T4), Triiodothyronine (T3)... 

D6 2.5 18.8 codeine, desipramine, dextromethorphan, fluoxetine, haloperidol, imipramine quinidine, ajmaline... 

An isolated report describes cardiac failure in a patient given aj-maiine with Udocaine. Quinidine causes a very considerable increase in the plasma levels of ajmaline, and phenobarbital appears to cause a marked reduction. 

A study in 4 healthy subjects found that if a single 200-mg oral dose of quinidine was given with a single 50-mg oral dose of ajmaline, the AUC of ajmaline was increased 10- to 30-fold and the maximum plasma concentrations increased from 18 to 141 nanograms/mL. Another single-dose... 

Hori R, Okumura K, Inui K-I, Yasuhara M, Yamada K, Sakurai T, Kawai C. Quinidine-in-duced rise in ajmaline plasma concentration. JPharm Pharmacol (1984) 36, 202-4. 

Antiarrhythmics, class la (ajmaline, cibenzoline, disop/ramide, hydroquinidine, procainamide, quinidine) Chlorpromazine (rare case reports of torsade de pointes)... 

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