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Toxicol Ind Health. 2015 Dec;31(12):1325-33. doi: 10.1177/0748233713491814. Epub 2013 Jul 10.

Effects of tramadol, clonazepam, and their combination on brain mitochondrial complexes.

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Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt
Forensic Medicine and Clinical toxicology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt.


The present study is an unsubstantiated qualitative assessment of the abused drugs-tramadol and clonazepam. The aim of this study is to evaluate whether the effects of tramadol, clonazepam, and their combination on mitochondrial electron transport chain (ETC) complexes were influential at therapeutic or at progressively increasing doses. The study comprised of a total of 70 healthy male rats, aged 3 months. According to the drug intake regimen, animals were divided into seven groups: control, tramadol therapeutic, clonazepam therapeutic, combination therapeutic, tramadol abuse, clonazepam abuse, and combination abuse group. At the end of the experiment, brain mitochondrial ETC complexes (I, II, III, and IV) were evaluated. Histopathological examinations were also performed on brain tissues. The results showed that groups that received tramadol (therapeutic and abuse) suffered from weight loss. Tramadol abuse group and combination abuse group showed significant decrease in the activities of I, III, and IV complexes but not in the activity of complex II. In conclusion, tramadol but not clonazepam has been found to partially inhibit the activities of respiratory chain complexes I, III, and IV but not the activity of complex II and such inhibition occurred only at doses that exceeded the maximum recommended adult human daily therapeutic doses. This result explains the clinical and histopathological effects of tramadol, such as seizures and red neurons (marker for apoptosis), respectively.


Tramadol; abuse; clonazepam; mitochondrial electron transport

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