title: Behavioral and antioxidant activity of a tosylbenz[g]indolamine derivative. A proposed better profile for a potential antipsychotic agent.
abstract: BACKGROUND: Tardive dyskinesia (TD) is a major limitation of older antipsychotics. Newer antipsychotics have various other side effects such as weight gain, hyperglycemia, etc. In a previous study we have shown that an indolamine molecule expresses a moderate binding affinity at the dopamine D2 and serotonin 5-HT1A receptors in in vitro competition binding assays. In the present work, we tested its p-toluenesulfonyl derivative (TPBIA) for behavioral effects in rats, related to interactions with central dopamine receptors and its antioxidant activity. METHODS: Adult male Fischer-344 rats grouped as: i) Untreated rats: TPBIA was administered i.p. in various doses ii) Apomorphine-treated rats: were treated with apomorphine (1 mg kg-1, i.p.) 10 min after the administration of TPBIA. Afterwards the rats were placed individually in the activity cage and their motor behaviour was recorded for the next 30 min The antioxidant potential of TPBIA was investigated in the model of in vitro non enzymatic lipid peroxidation. RESULTS: i) In non-pretreated rats, TPBIA reduces the activity by 39 and 82% respectively, ii) In apomorphine pretreated rats, TPBIA reverses the hyperactivity and stereotype behaviour induced by apomorphine. Also TPBIA completely inhibits the peroxidation of rat liver microsome preparations at concentrations of 0.5, 0.25 and 0.1 mM. CONCLUSION: TPBIA exerts dopamine antagonistic activity in the central nervous system. In addition, its antioxidant effect is a desirable property, since TD has been partially attributed, to oxidative stress. Further research is needed to test whether TPBIA may be used as an antipsychotic agent.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, 54124 Greece. chzika@pharm.auth.gr
authors.forename: Chara A
authors.initials: CA
authors.lastname: Zika
authors.forename: Ioannis
authors.initials: I
authors.lastname: Nicolaou
authors.forename: Antonis
authors.initials: A
authors.lastname: Gavalas
authors.forename: George V
authors.initials: GV
authors.lastname: Rekatas
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Tani
authors.forename: Vassilis J
authors.initials: VJ
authors.lastname: Demopoulos