摘要:

Analyses of randomised clinical trials have suggested that only in selective populations may antiarrhythmic drugs be effective in improving prognosis: therapy of cardiac arrhythmias, in contrast to other cardiovascular pathological conditions, has not been fully successful. The ideal treatment of arrhythmias should be guided by a sound understanding of the relative arrhythmogenic mechanisms and vulnerable parameters of the different arrhythmias. New model agents are pure class III agents, developed to fulfil these ideal characteristics and are now under active investigation (dofetilide, ibutilide, azimilide, ambasilide, E 4031, almokalant, sematilide, RP 58866 and tedisamil).

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

All the drugs appearing in the Adis Profile Summary table have been selected based on information contained inR&D InsightTM, a proprietary product of Adis International. As the emphasis ofDrugs in R&Dis on the clinical potential of new drugs, selection of agents for a full profile is based on the extensiveness of available data. Information on all drugs in clinical development, as identified fromR&D InsightTM, is included in the summary table. Information and/or profiles of agents in preclinical development may be included as appropriate.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Azimilide (NE 10064, Stedicor®) is a novel class III antiarrhythmic agent which blocks both the slowly-activating and the rapidly-activating components of the delayed rectifier outward potassium current. Procter and Gamble has submitted a New Drug Application to the US Food and Drug Administration for azimilide in the maintenance of sinus rhythm in patients with supraventricular arrhythmias. In addition, Procter and Gamble is sponsoring the Azimilide Post-Infarct Survival Evaluation (ALIVE) study, a multinational phase III trial expected to enrol 5900 post-myocardial infarction patients, at high risk of sudden death because of low heart rate variability and depressed left ventricular (LV) function, at 600 sites worldwide. Procter and Gamble has licensed development and marketing rights for azimilide in Asia to Tanabe Seiyaku, and azimilide is undergoing preclinical investigation in Japan.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;The propafenone analogue diprafenone is a sodium channel antagonist with &bgr;-blocking properties. It has local anaesthetic and combined class Ic and II antiarrhythmic properties, and is being developed by Helopharm (Germany) for use in supraventricular tachyarrhythmias. It has been licensed to Boehringer Ingelheim for Germany, where it is undergoing phase III clinical trials. Licenses to Schering AG and Yamanouchi have been discontinued.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Dofetilide (UK 68, UK 68798, Tikosyn®, Xelide®) is a cardioselective potassium channel antagonist that selectively blocks the rapidly-activating component of the delayed rectifier potassium current.[1] A methanesulfonanilide derivative, dofetilide is related to sotalol and sematilide. Dofetilide is under development with Pfizer as a broad spectrum ‘pure’ class III antiarrhythmic agent (it has no class I, II or IV effects), and has demonstrated a low incidence of proarrhythmia and no cardiac inhibitory effects. Dofetilide (Tikosyn®) has been recommended for approval by the US Food and Drug Administration for the conversion of atrial fibrillation (AF) or atrial flutter to sinus rhythm and maintenance of sinus rhythm. The drug is also undergoing phase III trials in Europe, Australia and Japan. Dofetilide is an investigational agent in Canada. Preclinical development in ischaemic heart disorders may be proceeding in Norway.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;E 4031, a potent class III antiarrhythmic agent, selectively blocks the rapidly activating component of the delayed rectifier potassium channel current (IKr). The drug is undergoing phase II trials with Eisai in Europe, and preclinical development in the USA. E 4031 may be most useful for the treatment of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome and for the prevention of malignant ventricular arrhythmias and sudden heart arrest.E 4031 is one of several ‘pure’ methanesulfonamide class III agents derived from dexosotalol hydrochloride, a group which includes dofetilide, ibutilide, MK 499, risotilide and UK 66914.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Landiolol (ONO 1011) is an ultra short-acting &bgr;-blocker which is structurally related to esmolol, but which is more potent and more selective. Landiolol is undergoing phase III clinical trials with Ono (Japan) for use in the treatment of emergency tachyarrhythmias, and for better control of heart rate during surgery. The compound is available for licensing worldwide.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;The pirenzepine derivative otenzepad (AFDX 116) is the first competitive muscarinic M2 antagonist that is cardioselective and suitable for clinical development.[ 1] It is less potent but better tolerated than the nonselective muscarinic antagonist atropine. Otenzepad was originally developed by Boehringer Ingelheim Pharma KG (Boehringer Ingelheim) in Germany. The parent company is developing oral and IV formulations of the drug for use in symptomatic bradycardia, sinus bradycardia, sick sinus syndrome and symptomatic arrhythmias after intoxication. Otenzepad is undergoing phase II clinical trials Japan. It was also being tested clinically in Germany, but no recent research has been reported. Otenzepad is the racemate of 2 enantiomers, and the (+)-enantiomer has demonstrated a marked potential for clinical efficacy.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Sematilide (CK 1752, CK 1752A, ZK 110516), a methysulfonylamino parasubstituted procainamide derivative, is a potent and selective potassium channel antagonist. Oral and IV formulations of sematilide are under development with Berlex Laboratories (Schering AG) as class III antiarrhythmic agents. Sematilide is in phase III clinical trials with Berlex Laboratories in the USA, and has been licensed to Hoechst Marion Roussel in Japan, where it is in phase II clinical trials. It is also available for licensing in Europe and the USA.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Tedisamil (KC 8857) is a potassium channel antagonist with bradycardic action and class III antiarrhythmic properties. Under development by Solvay, the drug is in phase III clinical trials in Europe for the treatment of ischaemic heart disorders. Tedisamil is produced as a capsule for oral administration.Studies of the cardiac and haemodynamic effects of tedisamil in patients with heart failure secondary to dilated cardiomyopathy have so far shown it to be unsuitable as a treatment, as tedisamil increased vascular resistance.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS