The genetically determined ability to metabolize debrisoquine(DBR) is related to risk of lung cancer and DBR hydroxylation exhibits wide inter-individual variation. In this study, 100 korean adults were tested for their ability to metabolize DBR. The DBR metabolic phonotype were determined by metabolic ratio (MR, DBR/4-HDBR) which is the percent dose excreted as unchanged DBR divided by the percent dose excreted as 4-hydro-xydebrisoqinne(4-HriBR) in a aliquots of an eight hour urine sample, after 10 mg DBR test dose administration. Analysis was performed on a capillary gas chromatography fitted with electron capture detector. The results were as follows; 1. Geometric mean or DBR MR was 0.32 in male, 0.27 in female, 0.30 in total and the distribution of log(MR) was seemed to follow normal distribution. 2. Metabolic ratio of DBR was higher in non-smoker and non-drinker than in smoker and drinker without any statistically significant difference. 3. None of personal factors was significantly related to DBR MR except age. 4. The DBR metabolic phonotype was extensive metabolizer(EM) 93, intermediate metabolizer (IM) 7 by traditional method and EM 98, IM 3 by Caporaso's method. The poor metabolizer (PM) phenotype was not found by either method. 5. Maximal expected PM phenotype was 0.36% by traditional method and 0.04% by Caporaso's method.
Adult ; Capillaries ; Chromatography, Gas ; Debrisoquin* ; Female ; Humans ; Hydroxylation ; Lung Neoplasms ; Male ; Metabolism* ; Pharmacogenetics ; Phenotype

The effect of Pheniramine(Avil), a histaminergic-1 receptor blocking agent presently employed in treating various allergic diseases on pressor actions of norepinephring(NE) and tyramine (TR) was studied in the rabbit. Pheniramine, when given into a femoral vein with a dose(3mg/kg) enough to block H1-receptor, potentiated markedly the pressor responses of NE and TR. The pressor action of NE augmented by pheniramine was not affected by additional adminstration of debrisoquin (Drenergic neuron blocker) or phenelzine(monoamine oxidase inhibitor) or desipramine(U1-uptake blocker), or while potentiated by additional treatment with chlorisondamine(ganglionic blocker)or reserpine(catecholamine depleter). The hypertensive response of NE to phenelzine or desipramine was reinforced significantly by addition of pheniramine, but the response of NE in rabbits treated with reserpine or chlorisondamine or debrisoquin was not influenced by pheniramine-addition. Elevation of blood pressure to TR potentiated by pheniramine was attenuated significantly by reserpine treatment with chlorisondamine made the significant augmentation of pressor action to TR after pheniramine. Tyramine-induced response of blood pressure after pheniramine, but the response of blood pressure to TR caused by phenelzine or desipramine was enhanced markedly by pheniramine-treatment. From the above experimental results, it is thought that the pressor effect of NE and TR potentiated by pheniramine is similar to that of debrisoquin, i.e. the sensitization of effector cell, and that central action of pheniramine can not ruled out.
Blood Pressure ; Chlorisondamine ; Debrisoquin ; Desipramine ; Femoral Vein ; Neurons ; Norepinephrine* ; Oxidoreductases ; Phenelzine ; Pheniramine ; Rabbits ; Reserpine ; Tyramine*

Authors observed the antihypertensive effect of debrisoquin sulfate in 35 cases of essential hypertension and following results were obtained. 1) Results of short term control of blood pressure with debrisquin in 35 hypertensive patients revealed good control in 74.3%, fair in 14.3%, poor in 5.7% and failure in 5.7% of cases. Significant reduction of blood pressure was achieved in 7 of 9 cases of hypertension with addition of hydrochlorthiazide to debrisoquin. 2) During long term therapy with debrisoquin (duration of average 3.9 months), good control cases were slightly reduced(good in 58.6%, fair in 24.1%, poor in 6.9%, failure in 10.3%). But average effective dose of debriioquin was not increased significantly. 3) Antihypertensive effect of debrisoquin was slightly reduced in the cases of severe hypertension, hypertension of over 10 years duration and complication of cerebrovascular accident. 4) The side effects during treatment with debrisoquin were dizziness in 31.4%, headache in 11.4%, dry mouth, blurred vision, general weakness, insomnia in 8.6% respectively. There were no side effects in 48.6% of cases.
Blood Pressure ; Debrisoquin* ; Dizziness ; Headache ; Humans ; Hypertension* ; Mouth ; Sleep Initiation and Maintenance Disorders ; Stroke

BACKGROUND: Epidemiological studies have identified that positive family history and frequent exposures to environmental toxins such as 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) are of prime causative factors for PD. These toxins are mainly metabolized by MAO-B and CYP2D6. Thus, an individual with inherited defect in xenobiotic metabolism could have a higher susceptibility to PD. We performed this study to investigate a possible allelic association of MAO-B and CYP2D6 known to be involved in metabolism of dopamine and other drugs such as debrisoquine in PD. METHODS: We studied polymorphism of MAO-B and CYP2D6 genes in 69 sporadic idiopathic PD patients (31 males and 38 females) and 41 age-matched healthy control (20 males and 21 females) using genomic DNA extracted from peripheral blood white cell with polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP). RESULTS: There were eight different alleles of various numbers of GT repeats within the second intron of MAO-B. The frequency of (GT)20 allele was the highest (44.7%) in PD, while the frequencies of (GT)14 allele and (GT)19 allele were the highest in control groups. Furthermore, the odds ratios of (GT)16 allele and (GT)20 allele were 4.93 (95% confidence interval 0.6-107.63) and 6.15 (95% confidence interval; 2.52-15.51), respectively, suggesting a higher susceptibility to PD in (GT)20 allelic group (p<0.001). Polymorphism of CYP2D6 was also examined by PCR amplification followed by digestion with restriction enzymes. However, we were unable to identify G to A substitution at the junction of intron 3 and exon 4 nor base pair deletion in exon 5 from PD and control groups, which have been reported previously. CONCLUSIONS: These results suggest that the MAO-B gene polymorphism could serve as a determinant of genetic susceptibility to PD at least in Korean population. But the susceptibility may not be directly associated with polymorphism of CYP2D gene examined in this study.
Alleles ; Base Pairing ; Cytochrome P-450 CYP2D6* ; Cytochrome P-450 Enzyme System* ; Cytochromes* ; Debrisoquin ; Digestion ; DNA ; Dopamine ; Epidemiologic Studies ; Exons ; Genetic Predisposition to Disease ; Humans ; Introns ; Male ; Metabolism ; Monoamine Oxidase* ; Odds Ratio ; Parkinson Disease* ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length