Antidepressant-like and antinociceptive-like actions of 4-(4′-chlorophenyl)-6-(4″-methylphenyl)-2-hydrazinepyrimidine Mannich base in mice

• Published in: Pharmacology, biochemistry and behavior Vol. 82; no. 1; pp. 156 - 162
• Main Authors: Rodrigues, A.L.S., Rosa, J.M., Gadotti, V.M., Goulart, E.C., Santos, M.M., Silva, A.V., Sehnem, B., Rosa, L.S., Gonçalves, R.M., Corrêa, R., Santos, A.R.S.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2005; Elsevier Science
• Subjects: Abdomen; Acetic Acid - administration & dosage; Analgesics - pharmacology; Animals; Antidepressant; Antidepressive Agents - pharmacology; Behavior, Animal - drug effects; Biological and medical sciences; Female; Forced swimming test; Hydrazines - pharmacology; Male; Mannich base; Medical sciences; Mice; Monoaminergic system; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Pyrimidines - pharmacology; Swimming; Writhing test; Antidepressant; Forced swimming test; Monoaminergic system; Writhing test; Mannich base; Psychotropic; Rodentia; Stress; Mus domesticus; Vertebrata; Chemotherapy; Mammalia; Analgesic; Treatment; Antidepressant agent
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2005.08.003

This study investigated the possible antidepressant and antinociceptive action of CPMPH Mannich base, as well as the involvement of serotonergic, dopaminergic, noradrenergic and opioid systems and the l-arginine–nitric oxide pathway in the antidepressant-like effect of CPMPH in the forced swimming test (FST) in mice. The immobility time in the FST was significantly reduced by CPMPH (0.1–10 mg/kg, i.p.), without accompanying changes in the ambulation in an open-field. CPMPH at high doses (i.p. or s.c. routes) produced a significant inhibition of acetic acid-induced writhing. The antidepressant-like effect of CPMPH (1 mg/kg, i.p.) in the FST was prevented by pre-treatment of mice with methysergide (2 mg/kg, i.p., a non-selective serotonin receptor antagonist), sulpiride (32 mg/kg, i.p., a D 2 receptor antagonist) or yohimbine (1 mg/kg, i.p., an α 2-adrenoceptor antagonist). In contrast, the antidepressant-like effect of CPMPH was not affected by pre-treatment (i.p.) with naloxone (1 mg/kg, a non-selective opioid receptor antagonist) or l-arginine (750 mg/kg, a nitric oxide precursor). The results demonstrate that CPMPH had an antidepressant-like action that appears to be mediated through its interaction with serotonergic, dopaminergic and noradrenergic systems.