Abstract (EN):
Pindolol is an indolic drug that has been shown to enhance and/or accelerate selective serotonin specific reuptake inhibitors (SSRI)-induced antidepressant (AD) effect, even though the respective mechanism is still unclear. It has been demonstrated that inhibition of nitric oxide ((NO)-N-center dot) synthesis in CNS produces anxiolytic and AD-like behavioural effects in a variety of animal paradigms. On the other hand, sustained high levels of (NO)-N-center dot may be deleterious to CNS, predominantly due to the formation of peroxynitrite anion (ONOO-), which is generated via reaction of (NO)-N-center dot with superoxide radical (O-2(center dot-)). Therefore, the purpose of the present study was to characterize the putative pindolol scavenging effect on (NO)-N-center dot, ONOO-, and O-2(center dot-), using in vitro non-cellular systems. The obtained results clearly show that pindolol is a potent scavenger of (NO)-N-center dot (IC50 of 449 +/- 33 mu M) and ONOO- (IC50 of 131 +/- 24 mu M). Additionally, the scavenging effect of pindolol increased almost 8 times in the presence of 25 mM NaHCO3 (IC50 of 17 +/- 3 mu M), which indicates that pindolol efficiently scavenges reactive species that are produced from the ONOO-/CO2 reaction such as the nitrogen dioxide radical ((NO2)-N-center dot) and the carbonate radical anion (CO3 center dot-) These effects may contribute for the reduction of SSRI antidepressant latency that has been attributed to pindolol and may also constitute an additional value for this drug when depression is associated with pro-oxidant neurodegenerative diseases.
Idioma:
Inglês
Tipo (Avaliação Docente):
Científica
Contacto:
egracas@ff.up.pt
Nº de páginas:
10