21-Aminosteroid, or lazaroid, is one of a novel class of
antioxidant drugs designed to inhibit
iron-dependent lipid peroxidation in
biological lipid environments. They have shown promising results in several animal models of traumatic, ischemic and hemorrhagic injury of the central nervous system.
Neuroleptic-induced
orofacial dyskinesia is an animal model of
tardive dyskinesia whose pathophysiology has been related to oxidative stress in the basal ganglia. In this study, we have examined the protective role of
U-74500A [pregna-1,4,9(11)-triene-3,20-dione, 21-(4-(5,6-bis(diethylamino)-2-pyridinyl)-1-piperazinyl)-16-ethyl-HCl (16-alpha)], a 21-aminosteroid having
antioxidant property in attenuating the behavioral and biochemical effects of chronic
haloperidol and
chlorpromazine administration.
Haloperidol (1 mg/kg/day i.p.) and
chlorpromazine (5 mg/kg/day i.p.) administered for 21 days caused a significant increase in vacuous chewing movements (VCMs), tongue protrusion (TP) and the number of facial twitchings (FT) observed on day 22.
U-74500A (1, 2 and 5 mg/kg i.p.), administered every day, along with
haloperidol (1 mg/kg/day i.p.) and
chlorpromazine (5 mg/kg/day), attenuated the increase of VCMs and related behaviors on day 22.
Haloperidol and
chlorpromazine significantly increased lipid peroxidation in various brain areas such as the cortex, striatum and subcortical parts characterized by an increase in MDA levels. The coadministration of
U-74500A limited the effect of
haloperidol and
chlorpromazine on MDA levels in the cortex and striatum but not in the subcortical parts.
U-74500A, an aminosteroid, may have
therapeutic use in typical
neuroleptic-induced
tardive dyskinesia-like effects.