ANTIDEPRESSANT EFFECT AFTER ACUTE AND SUBACUTE ADMINISTRATION OF NOVEL NSUBSTITUTED BENZAMIDES ON RESERPINEINDUCED DEPRESSION IN MICE.
CORNEL CHIRIŢĂ*, AURELIA NICOLETA CRISTEA, SIMONA
NEGREŞ, CRISTINA ELENA ZBÂRCEA, CRISTINA DANIELA
MARINECI
University of Medicine and Pharmacy „Carol Davila”, Faculty of
Pharmacy, Traian Vuia 6, Sect. 2, 020956, Bucharest, Romania
Pharmacology and Clinical Pharmacy Department
*corresponding author: chirita.cornel@gmail.com
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Abstract:
The new N-substituted benzamides are structurally related to tiapride, sulpiride or amisulpride, drugs with dual dose-dependent activity on dopaminergic receptors. At low therapeutical doses, these drugs act presynapticly by blocking D3 receptors, which leads to an increase of dopamine level in the synaptic cleft. This mechanism provides utility in the treatment of negative symptoms of schizophrenia and several forms of depression. At higher therapeutical doses, benzamides block postsynaptic D2 receptors, having antipsychotic activity on positive symptoms of schizophrenia.
In this paper we investigated the antidepressant activity of the new synthesized compounds after per os (p.o.) acute and subacute administration in mice with reserpine-induced depression. Pharmacological tests were the tail suspension test (TST) and the antagonism of reserpine-induced blepharoptosis.
In tail suspension test, one of the three investigated compounds had a significant antidepressant effect (P<0.05, ANOVA) after one administration. After eight administrations, two of three new benzamides showed a significant antidepressant effect (P<0.05, ANOVA). The same two compounds produced antagonism toward reserpine-induced ptosis in the mouse, the protection degree being 65.38%, respectively 88.46%.
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