PHARMACOLOGICAL EVALUATION OF ACUTE AND SUBACUTE TOXICITY AND ANTIDEPRESSANT EFFECT AFTER ACUTE
ADMINISTRATION OF NOVEL N-SUBSTITUTED BENZAMIDES.
CORNEL CHIRIŢĂ1*, AURELIA NICOLETA CRISTEA1,
MANUELLA MILITARU3, SIMONA NEGREŞ1, CRISTINA ELENA
ZBÂRCEA1, DIANA CAMELIA NUŢĂ2
University of Medicine and Pharmacy „Carol Davila”, Faculty of
Pharmacy, Traian Vuia 6, Sect. 2, 020956, Bucharest, Romania
1Pharmacology and Clinical Pharmacy Department
2Pharmaceutical Chemistry Department
3University of Agronomical Sciences and Veterinary Medicine, Faculty of
Veterinary Medicine, Pathological Anatomy Department
*corresponding author: chirita.cornel@gmail.com
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Abstract:
The new synthesized N-substituted-benzamides are structurally related to tiapride, sulpiride or amisulpride, drugs mainly used in the treatment of psychosis and depressive states. This dual activity is based on the dose-dependent antagonist properties towards dopamine receptors. At low antidepressant doses, benzamides preferentially block presynaptic dopamine D3 autoreceptors, that control dopamine synthesis and its release into synaptic cleft, whereas at higher antipsychotic doses, the blocking is moved towards postsynaptic dopamine D2 receptors.
Our objective was to investigate the acute and subacute toxicity of the new synthesized compounds on mice, followed by the antidepressant activity after intraperitoneally (i.p.) acute administration in non-depressed mice, using the forced swimming test (FST).
LD50 after i.p. and per os (p.o.) administration were determined on mice, values being close to those of other benzamides therapeutically used. The histopathological examination showed, for one compound, renal and hepatic toxicity in one of five examined samples.
FST evidenced a significant antidepressant effect (p<0.05, „t” Student test), for two of three compounds, when compared with the control group..
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