The effect of therapeutic drugs and other pharmacologic agents on activity of porphobilinogen deaminase, the enzyme that is deficient in intermittent acute porphyria
| Autor: | Peter V. Tishler |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Imipramine medicine.medical_specialty Erythrocytes Chlorpromazine Porphobilinogen deaminase Promethazine General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley chemistry.chemical_compound In vivo Internal medicine Porphobilinogen medicine Animals Humans General Pharmacology Toxicology and Pharmaceutics Diazepam biology Chemistry General Medicine Enzyme assay Rats Enzyme Activation Hydroxymethylbilane Synthase Endocrinology Lead Liver Lead acetate Phenobarbital Porphyria Acute Intermittent biology.protein medicine.drug |
| Zdroj: | Life Sciences. 65:207-214 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/s0024-3205(99)00237-4 |
| Popis: | Drugs and toxins precipitate life-threatening acute attacks in patients with intermittent acute porphyria. These materials may act by directly inhibiting enzyme activity, thus further reducing porphobilinogen (PBG) deaminase activity below the ca. 50% level that results from the gene defect. To test this, we studied the effects of drugs that precipitate acute attacks (lead, phenobarbital, griseofulvin, phenytoin, sulfanilamide, sulfisoxazole, 17alpha-ethinyl estradiol, 5beta-pregnan-3alpha-ol-20-one), drugs that are safe (lithium, magnesium, chlorpromazine, promethazine), and those with uncertain effects (ethyl alcohol, imipramine, diazepam, haloperidol) on activity of PBG deaminase in vitro and in vivo. In the in vitro studies, of PBG deaminase from human erythrocytes from normals and individuals with IAP, only lead (> or = .01 mM) inhibited enzyme activity. Chlorpromazine (> or = .01 mM), promethazine (> or = .01 mM) and imipramine (1 mM) seemed to increase enzyme activity. In most in vivo experiments, male rats were injected intraperitoneally with test material twice daily for 3 days and once on day four; and erythrocyte and hepatic PBG deaminase activity was assayed thereafter. Effects on enzyme activity were observed only with 17alpha-ethinyl estradiol (0.05 microg/kg/day; reduction of 11% in erythrocyte enzyme [NS], and of 20% in liver enzyme [P=.02]), and imipramine (12.5 mg/kg/day; reduction in erythrocyte enzyme activity of 13% [P |
| Databáze: | OpenAIRE |
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