RESUMO

A single i.v. dose (0.1 mmol Be2+/kg) of beryllium chloride prolonged the duration of pentobarbital-induced sleep and zoxazolamine-induced paralysis, in rats. The effects are correlated with changes of the pharmacokinetic parameters and with the in vitro inhibition of both aliphatic and aromatic hydroxylation of pentobarbital and zoxazolamine. In vitro N-demethylation of meperidine and aminopyrine was partially inhibited while O-demethylation of quinidine was unaffected by liver microsomes of rats pretreated with beryllium salt. The findings give clues that beryllium chloride inhibits some forms of cytochrome P-450, especially those responsible for hydroxylation of substrates, like pentobarbital and zoxazolamine.

Assuntos

Berílio/farmacologia , Microssomos Hepáticos/enzimologia , Animais , Comportamento Animal/efeitos dos fármacos , Berílio/administração & dosagem , Citocromos b5/metabolismo , Depressão Química , Hidroxilação , Injeções Intravenosas , Masculino , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Pentobarbital/sangue , Pentobarbital/farmacologia , Ratos , Ratos Endogâmicos , Reflexo/efeitos dos fármacos , Sono/efeitos dos fármacos , Zoxazolamina/sangue