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Provedor de dados:  Biol. Res.
País:  Chile
Título:  Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit
Autores:  TSUJITA,MIKI
SAKURABA,SHIGEKI
KURIBAYASHI,JUNYA
HOSOKAWA,YUKI
HATORI,EIKI
OKADA,YASUMASA
KASHIWAGI,MASANORI
TAKEDA,JUNZO
KUWANA,SHUN-ICHI
Data:  2007-01-01
Ano:  2007
Palavras-chave:  Morphine
Donepezil
Rabbit
Respiratory depression
Alzheimer's disease
Cholinesterase inhibitor
Resumo:  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
Tipo:  Journal article
Idioma:  Inglês
Identificador:  http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602007000400008
Editor:  Sociedad de Biología de Chile
Formato:  text/html
Fonte:  Biological Research v.40 n.3 2007
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