Title : Mechanism of the inhibitory action of phenelzine on microsomal drug metabolism.

Pub. Date : 1981 Oct

PMID : 7288604






7 Functional Relationships(s)
Download
Sentence
Compound Name
Protein Name
Organism
1 In vitro, the addition of phenelzine produced immediate decrease in cytochrome P-450. Phenelzine cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
2 This initial decrease was found to be due to the direct binding of phenelzine to the ferrous heme of cytochrome P-450. Phenelzine cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
3 Further decrease in cytochrome P-450 occurred upon incubation of microsomes with phenelzine in the presence of NADPH. Phenelzine cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
4 The decrease in cytochrome P-450 with concomitant loss of heme can be partially inhibited by a substrate (aminopyrine) or by an inhibitor (metyrapone) of the microsomal enzymes, indicating the possible involvement of the metabolism of phenelzine to a reactive intermediate. Phenelzine cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
5 The comparison of the effect of phenelzine to that of phenylhydrazine strengthened the possibility that a reactive metabolic intermediate of phenelzine can cause heme destruction in cytochrome P-450. Phenelzine cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
6 The comparison of the effect of phenelzine to that of phenylhydrazine strengthened the possibility that a reactive metabolic intermediate of phenelzine can cause heme destruction in cytochrome P-450. Phenelzine cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus
7 Thus, phenelzine exerts its inhibitory action on microsomal drug metabolism most likely by decreasing the cytochrome P-450 content largely through heme destruction. Phenelzine cytochrome P450, family 2, subfamily g, polypeptide 1 Rattus norvegicus