Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an...

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Autores principales:	TSUJITA,MIKI, SAKURABA,SHIGEKI, KURIBAYASHI,JUNYA, HOSOKAWA,YUKI, HATORI,EIKI, OKADA,YASUMASA, KASHIWAGI,MASANORI, TAKEDA,JUNZO, KUWANA,SHUN-ICHI
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2007
Materias:	morphine donepezil rabbit respiratory depression Alzheimer's disease cholinesterase inhibitor
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602007000400008
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spelling	oai:scielo:S0716-976020070004000082008-04-18Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbitTSUJITA,MIKISAKURABA,SHIGEKIKURIBAYASHI,JUNYAHOSOKAWA,YUKIHATORI,EIKIOKADA,YASUMASAKASHIWAGI,MASANORITAKEDA,JUNZOKUWANA,SHUN-ICHI morphine donepezil rabbit respiratory depression Alzheimer's disease cholinesterase inhibitor Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease) can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal C0(2). In the other experiment, apneic threshold PaC0(2) was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbitinfo:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.40 n.3 20072007-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602007000400008en10.4067/S0716-97602007000400008
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	morphine donepezil rabbit respiratory depression Alzheimer's disease cholinesterase inhibitor
spellingShingle	morphine donepezil rabbit respiratory depression Alzheimer's disease cholinesterase inhibitor TSUJITA,MIKI SAKURABA,SHIGEKI KURIBAYASHI,JUNYA HOSOKAWA,YUKI HATORI,EIKI OKADA,YASUMASA KASHIWAGI,MASANORI TAKEDA,JUNZO KUWANA,SHUN-ICHI Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit
description	Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease) can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal C0(2). In the other experiment, apneic threshold PaC0(2) was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbit
author	TSUJITA,MIKI SAKURABA,SHIGEKI KURIBAYASHI,JUNYA HOSOKAWA,YUKI HATORI,EIKI OKADA,YASUMASA KASHIWAGI,MASANORI TAKEDA,JUNZO KUWANA,SHUN-ICHI
author_facet	TSUJITA,MIKI SAKURABA,SHIGEKI KURIBAYASHI,JUNYA HOSOKAWA,YUKI HATORI,EIKI OKADA,YASUMASA KASHIWAGI,MASANORI TAKEDA,JUNZO KUWANA,SHUN-ICHI
author_sort	TSUJITA,MIKI
title	Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit
title_short	Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit
title_full	Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit
title_fullStr	Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit
title_full_unstemmed	Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit
title_sort	antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit
publisher	Sociedad de Biología de Chile
publishDate	2007
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602007000400008
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Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

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