The antioxidant properties of clozapine and other related molecules we
re evaluated with the crocin bleaching test both in aqueous and non-aq
ueous environment. The tests of microsomal lipid peroxidation and carb
onyl formation were also used. In aqueous solution, chlorpromazine and
trifluoperazine appear particularly effective in the bleaching of cro
cin, while serotonin has an efficacy intermediate between those of phe
nothiazines and clozapine. The latter drug, on the other hand, in a no
n-aqueous medium shows an antioxidant power comparable to that of buty
lated hydroxytoluene, indicating that its antioxidant properties are b
etter expressed in a hydrophobic environment of the type present in a
biological membrane. In fact, in lipid peroxidation induced in microso
mal membranes, clozapine, chlorpromazine, trifluoperazine and serotoni
n act as very good antioxidants; at low concentrations, clozapine appe
ars to be the most efficient after butylated hydroxytoluene. Similarly
, all these compounds markedly inhibit protein carbonyl formation, clo
zapine being one of the most efficient. Thus, under different in vitro
experimental conditions, the neuroleptic drugs chlorpromazine and tri
fluoperazine and the antipsychotic substance clozapine act as very eff
ective antioxidants; this property might, at least in part, be respons
ible for the physiological and clinical effects observed il vivo.