Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit
Biol. Res
;
40(3): 339-346, 2007. graf
Artigo
em Inglês
| LILACS
| ID: lil-481311
ABSTRACT
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.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Piperidinas
/
Respiração
/
Inibidores da Colinesterase
/
Indanos
/
Morfina
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Inglês
Revista:
Biol. Res
Assunto da revista:
Biologia
Ano de publicação:
2007
Tipo de documento:
Artigo
País de afiliação:
Japão
Instituição/País de afiliação:
Keio University/JP
/
Kitasato Institute/JP
/
Teikyo University/JP
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