Activity on the CNS and antioxidant profile of two benzo[g]indolamine derivatives

Benzo[g]indolamines 1 and 2, designed as heterocyclic bioisosteres of the p henolic dopaminergic agonist 5-OH-DPAT (3), were evaluated for their CNS an d antioxidant activities. Compounds 1 and 2 resemble a conformation of 3 in which the OH hydrogen points toward the cyclohexane ring. Compound 1, expr essing a moderate binding affinity at the dopamine D-2 and serotonin 5-HT1A receptors in in vitro competition binding assays, acted in vivo as a parti al dopaminergic agonist as judged by its behavioural effects on experimenta l animals. Compound 2 expressed no binding affinity at either of the recept ors examined. However, it antagonized in vivo apomorphine effects, an activ ity usually associated with dopamine receptor antagonists. Both 1 and 2 are active inhibitors of lipid peroxidation while they scavenge hydroxyl radic als with potency similar to that of DMSO.