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

David C Henshall1, Nick D&uuml;rm&uuml;ller2, H Steve White3, Robert Williams4, Paul Moser2, Mark Dunleavy1, Peter H Silverstone51Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland; 2Porsolt and Partners Pharmacology, Le Genest-Saint-I...

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Autores principales:	David C Henshall, Nick D&uuml;rm&uuml;ller, H Steve White, Robert Williams,&nbsp;et al.
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2009
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/b93c28547b9c497ba789d052ac3f33bc
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spelling	oai:doaj.org-article:b93c28547b9c497ba789d052ac3f33bc2021-12-02T02:35:20ZElectroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents1176-63281178-2021https://doaj.org/article/b93c28547b9c497ba789d052ac3f33bc2009-03-01T00:00:00Zhttp://www.dovepress.com/electroencephalographic-and-behavioral-convulsant-effects-of-hydrobrom-a2947https://doaj.org/toc/1176-6328https://doaj.org/toc/1178-2021David C Henshall1, Nick D&uuml;rm&uuml;ller2, H Steve White3, Robert Williams4, Paul Moser2, Mark Dunleavy1, Peter H Silverstone51Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland; 2Porsolt and Partners Pharmacology, Le Genest-Saint-Isle, France; 3NeuroAdjuvants, Inc., Salt Lake City, UT, USA; 4Biovail Technologies, Ltd., Dublin, Ireland; 5Biovail Corporation, Mississauga, ON, Canada&nbsp;Abstract: A novel bromide salt of the antidepressant bupropion (bupropion HBr) has recently been developed and approved for use in the United States. Given previous use of bromides to treat seizures, and that the existing chloride salt of bupropion (HCl) can cause seizures, it is important to determine if the HBr salt may be less likely to cause seizures than the HCl salt. In the present animal studies this was evaluated by means of quantified electroencephalogram (EEG), observation, and the rotarod test in mice and rats. Both bupropion salts were tested at increasing equimolar doses administered intraperitoneally. The results in mice showed that bupropion HCl 125 mg/kg induced a significantly higher ten-fold increase in the mean number of cortical EEG seizures compared to bupropion HBr (7.50 &plusmn; 2.56 vs 0.75 &plusmn; 0.96; p = 0.045), but neither drug caused any brain injuries. In rats bupropion HBr 100 mg/kg induced single EEG seizure activity in the cortical and hippocampal (depth) electrodes and in signifi cantly (p &lt;&nbsp;0.05) fewer rats (44%) compared to bupropion HCl, which induced 1 to 4 convulsions per rat in all rats (100%) dosed. The total duration of cortical seizures in bupropion HCl-treated rats was significantly longer than the corresponding values obtained in bupropion HBr-treated rats (424.6 seconds vs 124.5 seconds respectively, p &lt; 0.05). Bupropion HCl consistently induced more severe convulsions at each dose level compared to bupropion HBr. Both treatments demonstrated a similar dose-dependent impairment of rotarod performance in mice. In conclusion, these findings suggest that bupropion HBr may have a significantly lower potential to induce seizures in mice and rats, particularly at higher doses, compared to bupropion HCl. Determination of this potential clinical advantage will require human studies. If confirmed by such studies, it is likely that this potential beneficial clinical benefit would be due to the presence of the bromide salt given the long history of the use of bromide to treat seizure disorders.Keywords: bupropion hydrobromide, bupropion hydrochloride, EEG, seizures, mice, rats, motor impairment David C HenshallNick D&uuml;rm&uuml;llerH Steve WhiteRobert Williams,&nbsp;et al.Dove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2009, Iss default, Pp 189-206 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 David C Henshall Nick D&uuml;rm&uuml;ller H Steve White Robert Williams,&nbsp;et al. Electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents
description	David C Henshall1, Nick D&uuml;rm&uuml;ller2, H Steve White3, Robert Williams4, Paul Moser2, Mark Dunleavy1, Peter H Silverstone51Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland; 2Porsolt and Partners Pharmacology, Le Genest-Saint-Isle, France; 3NeuroAdjuvants, Inc., Salt Lake City, UT, USA; 4Biovail Technologies, Ltd., Dublin, Ireland; 5Biovail Corporation, Mississauga, ON, Canada&nbsp;Abstract: A novel bromide salt of the antidepressant bupropion (bupropion HBr) has recently been developed and approved for use in the United States. Given previous use of bromides to treat seizures, and that the existing chloride salt of bupropion (HCl) can cause seizures, it is important to determine if the HBr salt may be less likely to cause seizures than the HCl salt. In the present animal studies this was evaluated by means of quantified electroencephalogram (EEG), observation, and the rotarod test in mice and rats. Both bupropion salts were tested at increasing equimolar doses administered intraperitoneally. The results in mice showed that bupropion HCl 125 mg/kg induced a significantly higher ten-fold increase in the mean number of cortical EEG seizures compared to bupropion HBr (7.50 &plusmn; 2.56 vs 0.75 &plusmn; 0.96; p = 0.045), but neither drug caused any brain injuries. In rats bupropion HBr 100 mg/kg induced single EEG seizure activity in the cortical and hippocampal (depth) electrodes and in signifi cantly (p &lt;&nbsp;0.05) fewer rats (44%) compared to bupropion HCl, which induced 1 to 4 convulsions per rat in all rats (100%) dosed. The total duration of cortical seizures in bupropion HCl-treated rats was significantly longer than the corresponding values obtained in bupropion HBr-treated rats (424.6 seconds vs 124.5 seconds respectively, p &lt; 0.05). Bupropion HCl consistently induced more severe convulsions at each dose level compared to bupropion HBr. Both treatments demonstrated a similar dose-dependent impairment of rotarod performance in mice. In conclusion, these findings suggest that bupropion HBr may have a significantly lower potential to induce seizures in mice and rats, particularly at higher doses, compared to bupropion HCl. Determination of this potential clinical advantage will require human studies. If confirmed by such studies, it is likely that this potential beneficial clinical benefit would be due to the presence of the bromide salt given the long history of the use of bromide to treat seizure disorders.Keywords: bupropion hydrobromide, bupropion hydrochloride, EEG, seizures, mice, rats, motor impairment
format	article
author	David C Henshall Nick D&uuml;rm&uuml;ller H Steve White Robert Williams,&nbsp;et al.
author_facet	David C Henshall Nick D&uuml;rm&uuml;ller H Steve White Robert Williams,&nbsp;et al.
author_sort	David C Henshall
title	Electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents
title_short	Electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents
title_full	Electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents
title_fullStr	Electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents
title_full_unstemmed	Electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents
title_sort	electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents
publisher	Dove Medical Press
publishDate	2009
url	https://doaj.org/article/b93c28547b9c497ba789d052ac3f33bc
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Electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents

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