Abstract
A new series of pyridazin-3-one derivatives were designed, synthesized and evaluated for their preclinical antidepressant effect on Swiss mice. Among the series, compounds 6c, 6d and 6f exhibited significant activity profile in forced swimming test. Compounds 6c and 6d were most efficacious, which at dose of 50 mg kg−1 reduced the time of immobility by 42.85 and 38.09 %, respectively, as compared to the standard drug fluoxetine which reduced the immobility time by 45.23 % at the dose of 32 mg kg−1. All the test and standard compounds were administered orally 60 min before the test. Interestingly, all active compounds did not cause any significant alteration of locomotor activity in mice as compared to control, indicating that the hybrids did not produce any motor impairment effects. The results indicate that pyridazin-3(2H)-one derivatives may have potential therapeutic value for the management of mental depression.
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Abbreviations
- 1H NMR:
-
1H nuclear magnetic resonance
- CDCl3 :
-
Deuterated chloroform
- CHCl3 :
-
Chloroform
- CNS:
-
Central nervous system
- DMF:
-
Dimethylformamide
- DMSOd6 :
-
Deuterated dimethylsulfoxide
- ESI:
-
Electrospray ionization
- FST:
-
Forced swimming test
- HCl:
-
Chlohydric acid
- IR:
-
Infrared
- KBr:
-
Potassium bromide
- LD:
-
Lethal dose
- MAOIs:
-
Monoamine oxidase inhibitors
- MDD:
-
Major depression disorder
- NaOH:
-
Potassium hydroxide
- SNRIs:
-
Serotonin–norepinephrine reuptake inhibitors
- SSRIs:
-
Selective serotonin reuptake inhibitors
- TCAs:
-
Tricyclic antidepressants
- TMS:
-
Tetramethylsilane
- TRI:
-
Triple reuptake inhibitors
- USFDA:
-
United States Food and Drug Administration
- WHO:
-
World Health Organization
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Acknowledgments
The authors are grateful to the University Mohammed V and Laboratory of control of drugs, Rabat-Morocco, for, IR, RMN and MASS spectra and the studies of antidepressant activity.
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Boukharsa, Y., Meddah, B., Tiendrebeogo, R.Y. et al. Synthesis and antidepressant activity of 5-(benzo[b]furan-2-ylmethyl)-6-methylpyridazin-3(2H)-one derivatives. Med Chem Res 25, 494–500 (2016). https://doi.org/10.1007/s00044-015-1490-x
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DOI: https://doi.org/10.1007/s00044-015-1490-x