title: The effect of the spin trapping agent α-phenyl-n-tert-butyl nitrone on dexfenfluramine-induced serotonin depletion in rat brain.
abstract: Oxygen-free radical formation from either the parent compound amphetamine, its metabolites or drug-released serotonin (5-HT) has been implicated in the reduction of serotoninergic markers caused by amphetamine derivatives. Therefore, the present study investigated the effects of the spin-trapping agent α-phenyl-tert-butyl nitrone (PBN) on the 5-HT-lowering action of dexfenfluramine (DF) in rats, compared with p-chloroamphetamine (PCA). PBN (150 mg/kg, i.p, divided in two doses) almost totally prevented the reduction of 5-HT in particularly sensitive regions of the rat brain (cortex and striatum) 1 and 7 days after DF (10 mg/kg, i.p.). It also provided complete protection against the acute 5-HT-depleting action of PCA (5 mg/kg, i.p.), reducing it at 7 days in striatum, although with the higher dose (300 mg/kg, divided in two doses) there was a tendency to antagonize the long-term effects in both regions. With DF, however, the antagonistic effect of PBN was associated with a marked reduction of the plasma and brain concentrations of the parent drug, but particularly its active metabolite dexnorfenfluramine (DNF). Thus, reduced brain availability of the total active drug (DF+DNF) may explain why PBN prevents the neurochemical effects of DF (but not PCA), including the long-term one which possibly depends on the extent of the initial 5-HT lowering.
authors.affiliation: Istituto di Ricerche Farmacologiche `Mario Negri', via Eritrea 62, 20 157 Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bergami
authors.forename: C
authors.initials: C
authors.lastname: Fracasso
authors.forename: S
authors.initials: S
authors.lastname: Caccia