title: Pindolol is a potent scavenger of reactive nitrogen species.
abstract: 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) 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 may be deleterious to CNS, predominantly due to the formation of peroxynitrite anion (ONOO-), which is generated via reaction of *NO with superoxide radical (O2*-). Therefore, the purpose of the present study was to characterize the putative pindolol scavenging effect on *NO, ONOO-, and O2*-, using in vitro non-cellular systems. The obtained results clearly show that pindolol is a potent scavenger of *NO (IC50 of 449+/-33 microM) and ONOO- (IC50 of 131+/-24 microM). Additionally, the scavenging effect of pindolol increased almost 8 times in the presence of 25 mM NaHCO3 (IC50 of 17+/-3 microM), which indicates that pindolol efficiently scavenges reactive species that are produced from the ONOO-/CO2 reaction such as the nitrogen dioxide radical (*NO2) and the carbonate radical anion (CO3*-). 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.
authors.affiliation: REQUIMTE, Departamento de Química-Física, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4099-030 Porto, Portugal. egracas@ff.up.pt
authors.forename: Eduarda
authors.initials: E
authors.lastname: Fernandes
authors.forename: Ana
authors.initials: A
authors.lastname: Gomes
authors.forename: David
authors.initials: D
authors.lastname: Costa
authors.forename: José L F C
authors.initials: JL
authors.lastname: Lima
mesh_terms: D018687:Antidepressive Agents, Second-Generation / Q000378:metabolism; D005452:Fluoresceins; D020128:Inhibitory Concentration 50; D010869:Pindolol / Q000737:chemistry / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism; D017693:Sodium Bicarbonate / Q000378:metabolism
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005452:Fluoresceins; D010869:Pindolol; D026361:Reactive Nitrogen Species; D017367:Selective Serotonin Reuptake Inhibitors; D017693:Sodium Bicarbonate; C112456:4,5-diamino-2-(3,6-dihydroxy-9H-xanthen-9-yl)benzoic acid