Data/hora: 03/06/2024 07:52:46

Provedor de dados: | Biological Research
País: | Chile
Título: | Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits
Autores: | SAKURABA,SHIGEKI; TSUJITA,MIKI; ARISAKA,HIROFUMI; TAKEDA,JUNZO; YOSHIDA,KAZUICHI; KUWANA,SHUN-ICHI.
Data: | 2009-01-01
Ano: | 2009
Palavras-chave: | Buprenorphine; Donepezil; Rabbit; Respiratory depression; Cholinesterase inhibitor.
Resumo: | 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.
Tipo: | Journal article
Idioma: | Inglês
Identificador: | http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602009000400008
Editor: | Sociedad de Biología de Chile
Formato: | text/html
Fonte: | Biological Research  v.42 n.4 2009