BW A256C, a chemically novel class 1 antiarrhythmic agent. A comparison of <i>in vitro</i> and <i>in vivo</i> activity with other class 1 antiarrhythmic agents

Allan, Geoffrey; Donoghue, Stephen; Follenfant, M.J.; Sawyer, David A.

doi:10.1111/j.1476-5381.1986.tb10209.x

Cited by 5 publications

(6 citation statements)

References 22 publications

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“…Action potential duration and effective refractory period (ERP) are not significantly changed by BW A256C in the guinea pig ventricular muscle. However, in the dog Purkinje fibre both parameters are decreased in a concentration-dependent manner; this is attributable to an effect on the inward "window" current, camed by sodium ions, which contributes to maintenance of the plateau in Purkinje tissue (2,3,8). and 1.8 X Data show mean percentage changes & SEM for GPV (n = 6) and DPF (n = 5).…”

Section: Pharmacological Studies Electrophysiological Studies In Vitromentioning

confidence: 98%

“…However, unlike these agents, BW A256C is devoid of hypotensive activity at antiarrhythmic doses ( Table 4). When BW A256C is compared with flecainide in this preparation, it can be demonstrated that at equieffective antian-hythmic doses there is greater cardiovascular depression, as indicated by a reduction in blood pressure, heart rate, and atrioventricular conduction associated with the administration of flecainide (2).…”

Section: Inhibition Of Aconitine-induced Arrhythmias In Anaesthetisedmentioning

confidence: 99%

“…These changes are succeeded by the occurrence of multiple ventricular tachyarrhythmias, which occur at 5-10 min after occlusion. A second surge of ventricular arrhythmias occur at 12-20 min following occlusion (2,12,14). On reperfusion of the LAD after a l-h period of occlusion, there is an immediate phase of ventricular tachyarrhythmias that lasts for 5 min, which is then followed by a resurgence of ventricular tachyarrhythmias at 1 5-20 min following reperfusion.…”

Section: Suppression Of Coronary Artery Reperjiiion-induced Arrhythmimentioning

confidence: 99%

“…Effect ofpretreatment with quinidine, procainamide, lidocaine, flecainide, and B WA256C on the dose of aconitine required to induce ventricular arrhythmias in anaesthetised ratsReproduced from Allan et al(2). Data given as mean k SEM.…”

mentioning

confidence: 99%

“…occlusion and reperfusion. In this respect it is the most potent among a series of antiarrhythmic drugs studied (2).…”

mentioning

confidence: 99%

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BW A256C, a Chemically Novel Class 1C Antiarrhythmic Agent

Allan

Donoghue

1988

Cardiovascular Drug Reviews

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Class 1 antiarrhythmic agents have been demonstrated to suppress a variety of clinical arrhythmias; however, their efficacy in the prevention of sudden death has not been established (5). Failure in the management of life-threatening arrhythmias has arisen in part because of the limiting side-effects frequently associated with the use of these agents (22). Episodes of proarrhythmia, sometimes proving fatal, and more tolerable yet limiting side-effects associated with central nervous system penetration, e.g., giddiness, tremor, and convulsions, are quite common with these agents (1 3,18). To try to overcome some of the limitations of presently available antiarrhythmic therapy, we embarked on a programme of research directed toward the development of a novel antiarrhythmic agent with restricted access to the central nervous system. BW A256C [5(3)-a~no-6-(2,3-dichlorophenyl)-2,3(2,5)-dihydro-3-(5)-imino-2-isopropyl-1,2,4-triazine] is a chemically novel antiarrhythmic agent that reduces in a concentration-dependent fashion the sodium-dependent rate of rise of phase 0 of the cardiac action potential, an action described by Vaughan Williams as class 1 antiarrhythmic action ( 19). In this respect it is more potent than other class 1 agents such as quinidine, lidocaine, disopyramide, and flecainide (2). In common with other class 1 antiarrhythmic agents, the effects of BW A256C are use, frequency, and voltage dependent. However, unlike other agents, BW A256C has no effect on the duration of the action potential and its kinetics of onset of and recovery from use-dependent block are slower than for any previously reported class 1 agent (10). These distinctive properties place BW A256C in subclass 1 C in the present classification of antiarrhythmic agents (6).Pharmacological studies in vivo demonstrate that BW A256C prevents arrhythmogenesis induced chemically by aconitine administration or that induced by coronary

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Section: Pharmacological Studies Electrophysiological Studies In Vitromentioning

confidence: 98%

Section: Inhibition Of Aconitine-induced Arrhythmias In Anaesthetisedmentioning

confidence: 99%