Effect of pirenzepine on the N-demethylation of D(-)ephedrine and ethylmorphine by rabbit liver microsomes.
The possible interaction of pirenzepine with the mixed-function oxidases obtained from phenobarbital-pretreated rabbit microsomes was examined in vitro. Under experimental conditions that did not lead to its own N-demethylation, the drug inhibited the microsomal oxidase systems responsible for the N-demethylation of D(-)ephedrine and ethylmorphine. Kinetic studies showed that pirenzepine inhibited the metabolism of both drugs in a competitive manner. The results indicated that the observed pirenzepine stability to the hepatic N-demethylating system is not a result of low affinity of the drug to the system.
el-Obeid
H A
HA
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
al-Rashood
K A
KA
al-Khamees
H A
HA
al-Khamis
K I
KI
Mian
M S
MS
D000818:Animals; D003640:Dealkylation; D003864:Depression, Chemical; D004809:Ephedrine / Q000493:pharmacokinetics*; D005036:Ethylmorphine / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology*; D011817:Rabbits
D010890:Pirenzepine; D006899:Mixed Function Oxygenases; D004809:Ephedrine; D005036:Ethylmorphine; D010634:Phenobarbital