New dibenzazepine derivatives with disinhibitory and/or antidepressant potential: neurochemical and behavioural study in the open-field and forced swimming tests.
Original bioisosteric analogues of clozapine were evaluated for potential disinhibitory and/or antidepressant effects using the open-field test in the rat and Porsolt's forced swimming test in the mouse. Attempts to relate the behavioural results to the binding affinities for dopamine (D1, D2), serotonin (5-HT(2)) and muscarinic (M) receptors were also 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 antipsychotic 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 group 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 imipramine. While it was not possible to relate the first profile to any binding interaction, a relation could be established among the second group of compounds between the typical or atypical antipsychotic behavioural profile and the 5-HT(2)/D2 ratio.
Therabel Research s.a., Ch. D'Alsemberg, 1001, 1180 Brussels, Belgium.
J.
J
Bruhwyler
J.F.
JF
Liégeois
C.
C
Lejeune
F.
F
Rogister
J.
J
Delarge
J.
J
Géczy