Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits

Buprenorphine is a mixed opioid receptor agonist-antagonist used in acute and chronic pain management. Although this agent's analgesic effect increases in a dose-dependent manner, buprenorphine-induced respiratory depression shows a marked ceiling effect at higher doses, which is considered to...

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Autores principales:	SAKURABA,SHIGEKI, TSUJITA,MIKI, ARISAKA,HIROFUMI, TAKEDA,JUNZO, YOSHIDA,KAZUICHI, KUWANA,SHUN-ICHI
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2009
Materias:	buprenorphine donepezil rabbit respiratory depression cholinesterase inhibitor
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602009000400008
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spelling	oai:scielo:S0716-976020090004000082010-03-17Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbitsSAKURABA,SHIGEKITSUJITA,MIKIARISAKA,HIROFUMITAKEDA,JUNZOYOSHIDA,KAZUICHIKUWANA,SHUN-ICHI buprenorphine donepezil rabbit respiratory depression cholinesterase inhibitor Buprenorphine is a mixed opioid receptor agonist-antagonist used in acute and chronic pain management. Although this agent's analgesic effect increases in a dose-dependent manner, buprenorphine-induced respiratory depression shows a marked ceiling effect at higher doses, which is considered to be an indicator of safety. Nevertheless, cases of overdose mortality or severe respiratory depression associated with buprenorphine use have been reported. Naloxone can reverse buprenorphine-induced respiratory depression, but is slow-acting and unstable, meaning that new drug candidates able to specifically antagonize buprenorphine-induced respiratory depression are needed in order to enable maximal analgesic effect without respiratory depression. Acetylcholine is an excitatory neurotransmitter in central respiratory control. We previously showed that a long-acting acetylcholinesterase inhibitor, donepezil, antagonizes morphine-induced respiratory depression. We have now investigated how donepezil affects buprenorphine-induced respiratory depression in anesthetized, paralyzed, and artificially ventilated rabbits. We measured phrenic nerve discharge as an Índex of respiratory rate and amplitude, and compared discharges following the injection of buprenorphine with discharges following the injection of donepezil. Buprenorphine-induced suppression of the respiratory rate and respiratory amplitude was antagonized by donepezil (78.4 ± 4.8 %, 92.3% ± 22.8 % of control, respectively). These findings indicate that systemically administered donepezil restores buprenorphine-induced respiratory depression in anesthetized rabbits.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.42 n.4 20092009-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602009000400008en10.4067/S0716-97602009000400008
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	buprenorphine donepezil rabbit respiratory depression cholinesterase inhibitor
spellingShingle	buprenorphine donepezil rabbit respiratory depression cholinesterase inhibitor SAKURABA,SHIGEKI TSUJITA,MIKI ARISAKA,HIROFUMI TAKEDA,JUNZO YOSHIDA,KAZUICHI KUWANA,SHUN-ICHI Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits
description	Buprenorphine is a mixed opioid receptor agonist-antagonist used in acute and chronic pain management. Although this agent's analgesic effect increases in a dose-dependent manner, buprenorphine-induced respiratory depression shows a marked ceiling effect at higher doses, which is considered to be an indicator of safety. Nevertheless, cases of overdose mortality or severe respiratory depression associated with buprenorphine use have been reported. Naloxone can reverse buprenorphine-induced respiratory depression, but is slow-acting and unstable, meaning that new drug candidates able to specifically antagonize buprenorphine-induced respiratory depression are needed in order to enable maximal analgesic effect without respiratory depression. Acetylcholine is an excitatory neurotransmitter in central respiratory control. We previously showed that a long-acting acetylcholinesterase inhibitor, donepezil, antagonizes morphine-induced respiratory depression. We have now investigated how donepezil affects buprenorphine-induced respiratory depression in anesthetized, paralyzed, and artificially ventilated rabbits. We measured phrenic nerve discharge as an Índex of respiratory rate and amplitude, and compared discharges following the injection of buprenorphine with discharges following the injection of donepezil. Buprenorphine-induced suppression of the respiratory rate and respiratory amplitude was antagonized by donepezil (78.4 ± 4.8 %, 92.3% ± 22.8 % of control, respectively). These findings indicate that systemically administered donepezil restores buprenorphine-induced respiratory depression in anesthetized rabbits.
author	SAKURABA,SHIGEKI TSUJITA,MIKI ARISAKA,HIROFUMI TAKEDA,JUNZO YOSHIDA,KAZUICHI KUWANA,SHUN-ICHI
author_facet	SAKURABA,SHIGEKI TSUJITA,MIKI ARISAKA,HIROFUMI TAKEDA,JUNZO YOSHIDA,KAZUICHI KUWANA,SHUN-ICHI
author_sort	SAKURABA,SHIGEKI
title	Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits
title_short	Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits
title_full	Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits
title_fullStr	Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits
title_full_unstemmed	Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits
title_sort	donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits
publisher	Sociedad de Biología de Chile
publishDate	2009
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602009000400008
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Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits

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