کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5553669 | 1557957 | 2017 | 8 صفحه PDF | دانلود رایگان |
Depression is a devastating disorder which has a high impact on the wellbeing of overall society. As such, need for innovative therapeutic agents are always there. Most of the researchers focused on N-methyl-d-aspartate receptor to explore the antidepressant like activity of new therapeutic agents. Dextromethorphan is a cough suppressant agent with potential antidepressant activity reported in mouse force swimming test. Considering N-methyl-d-aspartate as a forefront in exploring antidepressant agents, here we focused to unpin the antidepressant mechanism of dextromethorphan targeting N-methyl-d-aspartate receptor induced nitric oxide-cyclic guanosine monophosphate signaling. Dextromethorphan administered at a dose of 10 and 30Â mg/kg i.p significantly reduced the immobility time. Interestingly, this effect of drug (30Â mg/kg) was inhibited when the animals were pretreated either with N-methyl-d-aspartate (75Â mg/kg), or l-arginine (750Â mg/kg) as a nitric oxide precursor and/or sildenafil (5Â mg/kg) as a phosphodiesterase 5 inhibitor. However, the antidepressant effect of Dextromethorphan subeffective dose (3Â mg/kg) was augmented when the animals were administered with either L-NG-Nitroarginine methyl ester (10Â mg/kg) non-specific nitric oxide synthase inhibitor, 7-Nitroindazole (30Â mg/kg) specific neural nitric oxide synthase inhibitor, MK-801 (0.05Â mg/kg) an N-methyl-d-aspartate receptor antagonist but not aminoguanidine (50Â mg/kg) which is specific inducible nitric oxide synthase inhibitor as compared to the drugs when administered alone. No remarkable effect on locomotor activity was observed during open field test when the drugs were administered at the above mentioned doses. Therefore, it is evident that the antidepressant like effect of Dextromethorphan is owed due to its inhibitory effect on N-methyl-d-aspartate receptor and NO- Cyclic guanosine monophosphate pathway.
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Journal: Biomedicine & Pharmacotherapy - Volume 85, January 2017, Pages 627-634