Analgesia by dihydrocodeine is not due to formation of dihydromorphine: evidence from nociceptive activity in rat thalamus.
J Pharmacol Exp Ther
; 281(3): 1164-70, 1997 Jun.
Article
em En
| MEDLINE
| ID: mdl-9190849
ABSTRACT
Dihydrocodeine is increasingly used in slow-release preparations for the treatment of chronic pain on step 2 of the "analgesic ladder" of the World Health Organization. Dihydrocodeine is suggested to act after O-demethylation to dihydromorphine. To test this possibility, experiments were carried out on rats under urethane anesthesia in which nociceptive activity was evoked by electrical stimulation of afferent C fibers in the sural nerve and recorded from neurons in the ventrobasal complex of the thalamus. Dihydrocodeine administered by intravenous injection reduced the evoked nociceptive activity in a dose-dependent manner. Like morphine, dihydrocodeine was capable of completely suppressing the evoked activity. Maximum depression was caused by 2 mg/kg, and the ED50 is 0.47 mg/kg. Naloxone (0.2 mg/kg) reversed the effect of dihydrocodeine (2 mg/kg). To inhibit O-demethylation of dihydrocodeine to dihydromorphine, metyrapone or cimetidine (50 mg/kg) was injected intraperitoneally 20 min before dihydrocodeine (1 and 2 mg/kg). This failed to markedly reduce the effect of dihydrocodeine. Dihydromorphine injected intravenously also reduced the evoked activity in a dose-dependent way. Maximum depression occurred at a dose of 4 mg/kg, and the ED50 is 0.97 mg/kg. Dihydrocodeine and dihydromorphine were equieffective when administered by intrathecal injection at a dose of 100 microg. It is concluded that dihydrocodeine causes analgesia independent of biotransformation to dihydromorphine.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tálamo
/
Codeína
/
Analgésicos Opioides
Limite:
Animals
Idioma:
En
Revista:
J Pharmacol Exp Ther
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Alemanha