Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits
Biol. Res
;
42(4): 469-475, 2009. ilus, graf
Artículo
en Inglés
| LILACS
| ID: lil-537106
ABSTRACT
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 percent, 92.3 percent ± 22.8 percent of control, respectively). These findings indicate that systemically administered donepezil restores buprenorphine-induced respiratory depression in anesthetized rabbits.
Texto completo:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
Nervio Frénico
/
Piperidinas
/
Insuficiencia Respiratoria
/
Buprenorfina
/
Inhibidores de la Colinesterasa
/
Indanos
/
Antagonistas de Narcóticos
Límite:
Animales
Idioma:
Inglés
Revista:
Biol. Res
Asunto de la revista:
Biologia
Año:
2009
Tipo del documento:
Artículo
/
Documento de proyecto
País de afiliación:
Japón
Institución/País de afiliación:
Kanagawa Dental College/JP
/
Keio University/JP
/
Uekusa Gakuen University/JP
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