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.
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.
Duarte
Filipe Silveira
FS
Laboratory of Neuropharmacology, Department of Pharmacology, CCB, Universidade Federal de Santa Catarina, Florianópolis, SC 88049-900, Brazil.
Codeço Martins
Paulo Roberto
PR
Romeiro
Gilberto Alves
GA
Monteiro De Lima
Thereza Christina
TC
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
D000588:Amines; D000928:Antidepressive Agents; D003508:Cycloheptanes