title: Antidepressant-like and antinociceptive-like actions of 4-(4'-chlorophenyl)-6-(4''-methylphenyl)-2-hydrazinepyrimidine Mannich base in mice.
abstract: 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 D2 receptor antagonist) or yohimbine (1 mg/kg, i.p., an alpha2-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.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis 88040-900, SC, Brazil.
authors.forename: A L S
authors.initials: AL
authors.lastname: Rodrigues
authors.forename: J M
authors.initials: JM
authors.lastname: Rosa
authors.forename: V M
authors.initials: VM
authors.lastname: Gadotti
authors.forename: E C
authors.initials: EC
authors.lastname: Goulart
authors.forename: M M
authors.initials: MM
authors.lastname: Santos
authors.forename: A V
authors.initials: AV
authors.lastname: Silva
authors.forename: B
authors.initials: B
authors.lastname: Sehnem
authors.forename: L S
authors.initials: LS
authors.lastname: Rosa
authors.forename: R M
authors.initials: RM
authors.lastname: Gonçalves
authors.forename: R
authors.initials: R
authors.lastname: Corrêa
authors.forename: A R S
authors.initials: AR
authors.lastname: Santos
mesh_terms: D000005:Abdomen; D019342:Acetic Acid / Q000008:administration & dosage; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D005260:Female; D006834:Hydrazines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011743:Pyrimidines / Q000494:pharmacology*; D013550:Swimming
chemical_list: C507000:4-(4'-chlorophenyl)-6-(4''-methylphenyl)-2-hydrazinepyrimidine; D000700:Analgesics; D000928:Antidepressive Agents; D006834:Hydrazines; D011743:Pyrimidines; D019342:Acetic Acid