Mexiletine is a very well-known class IB antiarrhythmic drug, whose enantiomers differ in both pharmacodynamic and pharmacokinetic properties, the (R)-isomer being the eutomer on experimental arrhythmias and in binding studies on cardiac voltage-gated sodium channels. meta-Hydroxymexiletine (MHM) is a minor metabolite of mexiletine, which has demonstrated to be more potent than the parent compound. Herein we report the synthesis and biological evaluation of MHM enantiomers for their potential antiarrhythmic activity. The same stereoselectivity pattern observed for mexiletine was found for MHM: the (R)-enantiomer of MHM was the eutomer on ac-arrhythmia also showing a negative inotropism higher than the one displayed by mexiletine and, at the same time, a decreased vasorelaxant activity on guinea-pig left atrium and guinea-pig ileum longitudinal smooth muscle.

Searching for new antiarrhythmic agents: evaluation of meta-hydroxymexiletine enantiomers / Catalano A.; Budriesi R.; Bruno C.; Di Mola A.; Defrenza I.; Cavalluzzi M. M.; Micucci M.; Carocci A.; Franchini C.; Lentini G.. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - STAMPA. - 65:(2013), pp. 511-516. [10.1016/j.ejmech.2013.05.008]

Searching for new antiarrhythmic agents: evaluation of meta-hydroxymexiletine enantiomers.

BUDRIESI, ROBERTA;MICUCCI, MATTEO;
2013

Abstract

Mexiletine is a very well-known class IB antiarrhythmic drug, whose enantiomers differ in both pharmacodynamic and pharmacokinetic properties, the (R)-isomer being the eutomer on experimental arrhythmias and in binding studies on cardiac voltage-gated sodium channels. meta-Hydroxymexiletine (MHM) is a minor metabolite of mexiletine, which has demonstrated to be more potent than the parent compound. Herein we report the synthesis and biological evaluation of MHM enantiomers for their potential antiarrhythmic activity. The same stereoselectivity pattern observed for mexiletine was found for MHM: the (R)-enantiomer of MHM was the eutomer on ac-arrhythmia also showing a negative inotropism higher than the one displayed by mexiletine and, at the same time, a decreased vasorelaxant activity on guinea-pig left atrium and guinea-pig ileum longitudinal smooth muscle.
2013
Searching for new antiarrhythmic agents: evaluation of meta-hydroxymexiletine enantiomers / Catalano A.; Budriesi R.; Bruno C.; Di Mola A.; Defrenza I.; Cavalluzzi M. M.; Micucci M.; Carocci A.; Franchini C.; Lentini G.. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - STAMPA. - 65:(2013), pp. 511-516. [10.1016/j.ejmech.2013.05.008]
Catalano A.; Budriesi R.; Bruno C.; Di Mola A.; Defrenza I.; Cavalluzzi M. M.; Micucci M.; Carocci A.; Franchini C.; Lentini G.
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/393363
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 22
  • ???jsp.display-item.citation.isi??? 21
social impact