RESUMO
A variety of tropane derivatives 14a-g were prepared via the reaction of the alcohol analogs 12a and 12b with substituted fluorobenzenes 13a-f. The prepared compounds were tested for their activity and selectivity toward the norepinephrine transporter (NET) and serotonin transporter (SERT) using yohimbine-induced mortality and 5-hydroxytryptophan-induced neurotoxicity in mice, respectively. All the tested compounds were found to be NE and 5-HT reuptake inhibitors except 14d which exhibited selective 5-HT reuptake inhibition activity.
Assuntos
Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Norepinefrina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/síntese química , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Serotonina/farmacologia , Tropanos/síntese química , 5-Hidroxitriptofano/toxicidade , Antagonistas Adrenérgicos alfa/toxicidade , Animais , Citalopram/síntese química , Citalopram/química , Clomipramina/síntese química , Clomipramina/química , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Fluoxetina/síntese química , Fluoxetina/química , Camundongos , Estrutura Molecular , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de Serotonina/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Tropanos/química , Tropanos/farmacologia , Ioimbina/antagonistas & inibidores , Ioimbina/toxicidadeRESUMO
Ten new 3,5-diphenyl-2-pyrazoline derivatives were synthesised by reacting 1,3-diphenyl-2-propen-1-one with hydrazine hydrate. The chemical structures of the compounds were proved by means of their IR, 1H-NMR spectroscopic data and microanalyses. The antidepressant activities of these compounds were evaluated by the 'Porsolt Behavioural Despair Test' on Swiss-Webster mice. 3-(4-Methoxyphenyl)-5-(3,4-dimethoxyphenyl)-2-pyrazoline, 3-(4-methoxyphenyl)-5-(2-chloro-3,4-dimethoxyphenyl)-2-pyrazoline and 3-(4-chlorophenyl)-5-(2-chloro-3,4-dimethoxyphenyl)-2-pyrazoline reduced 41.94-48.62% immobility times at 100 mgkg(-1) dose level. In addition, it was found that 4-methoxy and 4-chloro substituents on the phenyl ring at position 3 of the pyrazoline ring increased the antidepressant activity; the replacement of these groups by bromo and methyl substituents decreased activity in mice.