Convulsant and anticonvulsant effects of bupropion in mice

Electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents

“…The absence of EEG seizure activity at the 10, 30, and 60 mg/kg doses in this rat model is consistent with a previous report that bupropion HCl 5-50 mg/kg IP did not produce any behavioral convulsions in mice 7 and with reports of bupropion-induced behavioral convulsions in mice in the dosage range 75-160 mg/kg IP. 7,8,30 Although there was no signifi cant difference in the mean duration of the fi rst seizure between the two treatments in the cortex and hippocampus, the total duration of the multiple seizures following bupropion HCl treatment 100 mg/kg were 341% and 399% longer in the cortex and hippocampus, respectively, compared to equimolar bupropion HBr treatment. In addition, all EEG seizure activity observed with both treatments were accompanied by simultaneous predominantly mild (facial clonus with or without forelimb clonus and rearing) behavioral convuslions, however, more rats in the bupropion HCl treatment group (70%) had mild convulsions (Racine 23 Class I -facial clonus) compared to the bupropion HBr treatment group (20%).…”

“…The demonstration of dose-dependent convulsions in the dosage range 100-150 mg/kg in this study is consistent with the results of previous studies in mice. 7,8,30 In addition, the CD 50 values of 103 and 110 mg/kg obtained in this study for bupropion HCl and bupropion HBr treatments, respectively, are similar to the values of 116.72 (CI: 107.95, 126.20) and 119.7 (CI: 104.1, 137.6) mg/kg reported previously for IP bupropion HCl administration in mice. 7,30 Also, single-dose bupropion HCl and bupropion HBr treatments induced a dose-dependent increase in the total number of convulsions, the mean convulsions per mouse, and in the intensity of convulsions (mild, moderate, and severe).…”

“…This was surprising because in previous studies with bupropion HCl in mice, a dose-dependent increase in behavioral seizure activity was demonstrated in the dosage range 75 to 160 mg/kg. 7,8,30 The reason for not detecting any EEG seizure activity even though profound behavioral convulsions were observed following the administration of 150 mg/kg of either salt, and at the 100, 115, and 135 mg/kg doses is not known. However, it may reside with subcortical pathway activation and inhibition and hence, future studies employing simultaneous cortical and depth electrode recordings may yield the explanations for the lack of EEG recordings with the cortical electrodes used in this study.…”

“…7,8 The precise mechanism of bupropion-induced seizures remains unknown. Recently, Biovail (Biovail Laboratories International SRL, St. Michael, Barbados) has developed a new extended-release tablet formulation of bupropion hydrobromide (HBr) for once-daily administration.…”

CNS Adverse Effects: From Functional Observation Battery/Irwin Tests to Electrophysiology

“…In addition, it is recognized that pro-convulsant compounds as identified with the PTZ assay, such as venlafaxine, fentanyl, or isoniazid, may also be convulsant when administered alone, and thus the PTZ assay can be used as an indirect preclinical measure of convulsant risk (Himmel 2008;Santos et al 2002). However, not all convulsant compounds cause pro-convulsant effects; the antidepressant bupropion which has a well-established seizurogenic potential in the clinic does not alter seizure threshold in the PTZ assay (Tutka et al 2004). The PTZ assay begins with the administration of the test article to rats or mice, followed by the timed intravenous infusion of PTZ.…”