Landiolol was launched as iv infusion for the treatment of tachyarrhythmia
during surgery. This structurally related derivative of esmolol can be synthesized in 3 linear
steps from 3-(4-hydroxyphenyl)propionic acid by successive esterification followed by
alkylation of the phenol function with (2S)-glycidyltosylate and opening of the resulting
epoxide by the appropriate amine. Landiolol is an ultra short acting PI-adrenergic blocker
more cardioselective (βI/β2 = 255) than esmolol (βi/β2 = 32). It showed 6-8 times greater
efficiency compared to esmolol in reducing isoproterenol-induced increase in heart rate
and ventricular contraction in anesthetized dogs. In clinical trials, landiolol was effective
against a variety of arrhythmias with efficacy seen in patients with atrial fibrillation,
proxysmal supraventricular tachycardia, ventricular tachycardia and premature complexes.
Landiolol produced a doserelated pharmacokinetic behavior, has a rapid onset of action
(10 min.) and is rapidly hydrolyzed to inactive acidic metabolites by esterases after iv
administration. This results in an ultra-short half-life (approx. 3 min.) and p-blocade,
allowing rapid termination of the drug effect by termination of infusion if side effects occur.
Hypertension was the most frequent adverse event and resolved in less than 30 min. after
drug withdrawal.
