Toxicological and EEG studies on tramadol addiction and withdrawal in man and rat

ABSTRACT

The toxicity of tramadol, a synthetic analogue of codeine, was studied on human addicts as well as experimentally in rats. The oral LD[50] of tramadol was found to be 250 mg/Kg b.w. Chronic administration of tramadol had a cortical depressant effect as evident from the shifting of the electroencephalographic [EEG] activity towards a reduction of the alpha waves and theta and delta frequencies develop, heralding the onset of sedation. A shift of EEG activity towards low voltage, faster activity was seen in all records 10 days after stopping human addicts to tramadol there were changes in EEG activity reported as increased amounts of delta and theta activity and a slowing of alpha activity. During the withdrawal phase, the interictal EEG showed generalized bursts of slow waves and spikes or spike-and-wave complexes. Such changes were transient, usually occurring within the first few days after withdrawal and persisting for 15-20 days. The EEG activity returned to the normal control level after 20 days of withdrawal. Tramadol intoxication, the pupils of patients were significantly constricted [3.5 mm in diameter] relative to controls [5 mm]. As withdrawal progressed, the pupils started and continued to dilate until, at the end of the 10 day period, the patients had significantly wider pupils than controls. Typical absorption spectrum of tramadol in the wavelength 275 nm was selected for detection and the Rf value of tramadol was 0.67