Flestolol: an ultra-short-acting beta-adrenergic blocking agent.

Area of Science:

• Pharmacology
• Cardiovascular Medicine

Background:

• Flestolol (ACC-9089) is a novel nonselective, competitive, ultra-short-acting beta-adrenergic blocking agent.
• It lacks intrinsic sympathomimetic activity and is rapidly metabolized by plasma esterases, with a half-life of approximately 6.5 minutes.

Purpose of the Study:

• To evaluate the safety, tolerability, and efficacy of flestolol.
• To assess its pharmacokinetic and pharmacodynamic properties, including dose-response relationships and reversibility.

Main Methods:

• Administration to healthy volunteers and patients with supraventricular tachyarrhythmia and unstable angina.
• Dose-ranging studies and long-term infusion studies (up to seven days).
• Measurement of blood concentrations, isoproterenol-induced tachycardia, and hemodynamic parameters.

Main Results:

• Flestolol was well tolerated in healthy volunteers and patients at effective beta-blocking doses.
• A linear relationship was observed between flestolol blood concentrations and the degree of beta-adrenergic blockade.
• The drug demonstrated dose-dependent attenuation of tachycardia and rapid reversal of effects within 30 minutes of discontinuation.

Conclusions:

• Flestolol is a potent, well-tolerated, ultra-short-acting beta-adrenergic blocking agent.
• It effectively reduces heart rate in supraventricular tachyarrhythmia and controls chest pain in unstable angina.
• Its rapid reversibility suggests potential utility in critical care settings, which is under investigation.