Antiarrythmics

Many 1,2,3,5-benzenetetrol derivatives are used mediciaaHy. For example, khellin [82-02-0] (65), which is a naturally occurring benzopyranone, is used as a coronary vasodilator and bronchodilator (233). Derivatives of khellin are effective local anesthetics and antiarrythmics (234). Similarly, amine derivatives (68) that are prepared from khellinone oxime (66) exhibit hypnotic, sedative, anticonvulsant, antiinflammatory, cardiac analeptic, diuretic, and antiulcerous activity (235) (see Analgesics, antipyretics, and antiinflammatory agents). 

Ropitoin (79) is an antiarrythmic compound containing a hydan-toin ring. Its synthesis is accomplished by alkylating 77 with chloride 78 with the aid of sodium methoxide. ... 

It will be recalled that certain local anesthetic amides, such as procainamide and lidocaine, are active antiarrythmic agents. Annelation of a second aromatic ring is consistent with bioactivity. Bunaftine (21) is such an agent, prepared simply from reaction of the acid chloride of 1-naphthoic acid and... 

Interestingly, when propranolol is quaternized with methyl chloride, it loses its p-blocker activity and becomes the antiarrythmic agent pranolium chloride (22).8... 

Fig. 4.n Structures of the monobasic antiarrythmic, diso-pyramide and the dibasic analogue disobutamide. 

Pindolol, like nadolol, is a nonselective 8-adrenoblocker. It possesses antianginal, antihypotensive, and antiarrythmic action. It is used for arterial hypertension, angina stress (preventing attacks), supraventricular tachycardia, tachsystohc form of atrial fibrillation, and superventricular extrasystole. Synonyms of this drug are carvisken, visken, and others. 

Taurine (2-aminoethanesulfonic acid 4.235) is an inhibitory neurochemical that probably acts primarily as a neuromodulator rather than a neurotransmitter. It is formed from cysteine, and its accumulation can be prevented by the cardiac glycoside ouabain. Although receptor sites and specific actions cannot be elucidated without an antagonist, taurine has been implicated in epilepsy and, potentially, in heart disease. There are a large number of physiological effects attributed to taurine, among them cardiovascular (antiarrythmic), central (anticonvulsant, excitability modulation), muscle (membrane stabilizer), and reproductive (sperm motility factor) activity. Analogs of taurine, phthalimino-taurinamide (4.236) and its iV-alkyl derivatives, are less polar than taurine and are potent anticonvulsant molecules. 

Antiarrythmics, regulating the timing of heart muscle contraction and thus being useful in the treatment of heart rhythm irregularities which cause palpitations... 

This is primarily an anticonvulsant. Because of a wide range of toxic side effects its use as an antiarrythmic is limited to the treatment of arrhythmias caused by digitalis toxicity. Intravenous bolus injections can cause myocardial depression, hypotension, AV block and bradycardia. 

The antiarrythmic drug amiodarone inhibits reserpine binding in a concentration-dependent manner and has a sympatholytic, anti-adrenergic effect in the heart, inhibiting the uptake of norepinephrine (Haikerwal et al., 1999). Blockers of VMAT and L-type calcium channels have also been reported to exert reciprocal inhibitory actions (Mahata et al., 1996). 

After deglucosylation, the pathway proceeds through a 4,21-Dehydrogeissoschizine derivative to ajmalicine (an a-Blocking spasmolytic agent, used for tinnitus and cranial trauma with an ergot derivative). If cyclization occurs between C-17 and C-18, the yohimbine nucleus is produced, whose derivatives include the Rauvolfia alkaloids reserpine and resdnnamine (antihypertensive activity). Ajmaline, formerly used as an antiarrythmic, also occurs in Rauvolfia species, and several of the enzymes in the pathway have been isolated. Recent considerations suggest that the C-16-C-5 bond may be formed before the N-4-C-21 bond (Fig. 38). 

Buchert, E. Woosley, R.L. Chnical implications of variable antiarrythmic drug metabohsm. Pharmacogenetics 1992, 2, 2-11. 

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