title: Antidepressant-like profile of action of two 4-amine derivatives of 10,11-dihydro-5H-dibenzo [a,d] cycloheptane in mice evaluated in the forced swimming test.
abstract: This study investigated the antidepressant-like effect of 4-amine derivatives of 10,11-dihydro-5H-dibenzo-alkylamine-cycloheptane, 4-amine (3-N,N-dimethylpropylamine)-10,11-dihydro-5H-dibenzo[a,d]cycloheptane-5-one (ADDCH1) and 1,2,3,4,8,9-hexahydro-dibenzocyclohepta[4,4a,5-ef]1,4-diazepin (ADDCH2), in a validated experimental model of depression, the forced swimming test (FST) in mice. Female adult mice were sub-chronically (three doses in 24 h) or repeatedly (once a day for 10 days) treated with either of the compounds and evaluated in the FST. The sub-chronic treatment promoted a dose-dependent reduction in the immobility time in the FST with the doses of 50 mg/kg (ADDCH1) and 30 mg/kg (ADDCH2) ip being the most effective (33% and 37% of reduction, respectively). A similar profile of action was observed in the animals repeatedly treated with ADDCH1 50 mg/kg or ADDCH2 30 mg/kg ip (for 10 days) and there was no sign of motor impairment or locomotor activation as evaluated in the rota-rod and open-field tests, respectively. These findings suggest that these amine derivatives of the system dibenzocycloheptane have an antidepressant-like action which could be of clinical interest and, therefore, deserves further investigation. In addition, putative underlying mechanisms of action are discussed.
authors.affiliation: Laboratory of Neuropharmacology, Department of Pharmacology, CCB, Universidade Federal de Santa Catarina, Florianópolis, SC 88049-900, Brazil.
authors.forename: Filipe Silveira
authors.initials: FS
authors.lastname: Duarte
authors.forename: Paulo Roberto
authors.initials: PR
authors.lastname: Codeço Martins
authors.forename: Gilberto Alves
authors.initials: GA
authors.lastname: Romeiro
authors.forename: Thereza Christina
authors.initials: TC
authors.lastname: Monteiro De Lima
mesh_terms: D000588:Amines; D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry* / Q000494:pharmacology*; D003508:Cycloheptanes; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D005080:Exercise Test; D005260:Female; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D013550:Swimming
chemical_list: D000588:Amines; D000928:Antidepressive Agents; D003508:Cycloheptanes