NEW DIBENZAZEPINE DERIVATIVES WITH DISINHIBITORY AND OR ANTIDEPRESSANT POTENTIAL - NEUROCHEMICAL AND BEHAVIORAL-STUDY IN THE OPEN-FIELD ANDFORCED SWIMMING TESTS/

Original bioisosteric analogues of clozapine were evaluated for potent ial disinhibitory and/or antidepressant effects using the open-field t est in the rat and Porsolt's forced swimming test in the mouse. Attemp ts to relate the behavioural results to the binding affinities for dop amine (D1, D2), serotonin (5-HT2) and muscarinic (M) receptors were al so undertaken. In the open-field test, two main profiles were observed . The first profile corresponded to disinhibitory molecules resembling diazepam and ritanserin. The second profile corresponded to antipsych otic compounds resembling either typical (haloperidol, clothiapine) or atypical (clozapine) neuroleptics. The results obtained in the forced swimming test confirmed the neuroleptic-like activity of the second g roup of compounds, while two compounds of the first group (JL 3 and JL 26) showed an antidepressant-like activity, JL 3 being as active as i mipramine. While it was not possible to relate the first profile to an y binding interaction, a relation could be established among the secon d group of compounds between the typical or atypical antipsychotic beh avioural profile and the 5-HT2/D2 ratio.