• YAKHAK HOEJI
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• v.30 no.3
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• pp.111-120
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• 1986

The influence of debrisoquine on pressor actions of norepinephrine (NE) and tyramine (TR) was investigated in rabbits. Debrisquine(D), in the doses of 1.0, 3.0 and 6.0.mu.g/kg, i.v. potentiated significantly the pressor actions of NE and TR, except the action of TR in the dose of 1.0mg/kg of debrisoquine. NE response potentiated by debrisoquine was not affected by tranylcypromine, a MAO inhabiter, or desipramine, a NE uptake blocking agent, but augmented by reserpine, a NE depleting agent, or bethanidine, a sympathetic neuronal blocking agent. NE response potentiated by tranylcypromine or desipramine was augmented by debrisoquine, while NE response potentiated by reserine or bethanidine was not affected by debrisoquine. TR response potentiated by debrisoquine was weakened by tranylcypromine, desipramine or reserpine, and not affected by bethanidine. TR response in rabbit pretreated with tranylcypromine, desipramine or reserpine was augmented by debrisoquine, but in rabbit pretreated with bethanidine was not affected by debrisoquine.

• YAKHAK HOEJI
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• v.25 no.1
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• pp.15-25
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• 1981

This study was attempted to investigate the action of debrisoquine, a sympathetic blocking agent presently employed in treating hypertension, on renal function and to elucidate the mechanism of its action. Debrisoquine, given intravenously, elicited increased urine flow, osmolar and free water clearances, along with marked increases in excretion of both sodium and potassium. Glomerular filtration rate also increased, but renal plasma flow tended to decrease, so that the filtration fraction tended to increase. Rates of reabsorption of sodium and potassium in renal tubules were also significantly diminished. The diuresis induced by debrisoquine was completely blocked by treatment with phentolamine and reserpine, and also markedly inhibited by acute renal denervation. Debrisoquine, when injected directly into a renal artery, produced antidiuretic effect and a reduction in urinary excretion of sodium and potassium, along with diminished renal plasma flow and increased filtration fraction. The above observations indicate that debrisoquine, when given intravenously, induces diuresis in the dog as a result of both diminished tubular reabsorption of electrolytes and of renal hemodynamic changes, which seem to be related to its inhibitory action of catecholamine-release from the sympathetic nerve endings.

• Journal of Pharmaceutical Investigation
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• v.14 no.2
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• pp.92-103
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• 1984

The action of debrisoquine on renal function in rabbits was studied. 1. When debrisoquine was given into ear vein, it did not affect on renal functin with smaller doses of 0.1 or 0.3mg/kg, while with higher dose of 1.0mg/kg it elicited the significant decrease of urine flow, renal plasma flow and glomerular filtration rate, and the increase of filtration fraction, and at the same time sodium excreted in urine, FENa (fractional excretion of sodium) and osmolar clearance were significantly decreased, and then it exhibited the increase of $K^+/Na^+$ ratio and no changes of $T^cH_2O$. 2. Debrisoquine (1.0mg/kg), when injected repeatedly into a vein, produced a more marked decrease of urine flow. 3. Debrisoquine induced-antidiuretic action was not affected by pretreatment with phentolamine (2mg/kg, i.v.), alpha-sympathetic blocking agent. 4. Debrisoquine given intracerebroventricularly did not produce a significant change on renal function in dose of 0.1mg/kg. These results suggest that debrisoquine produce the antidiuretic effect in rabbit, and the mechanism of its action is due to dual actions that are the decrease of hemodynamic effect and the facilitation of reabsorption of sodium in renal tubules.

• 대한예방의학회:학술대회논문집
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• 1993.10a
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• pp.47-48
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• 1993

• Journal of Preventive Medicine and Public Health
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• v.27 no.3 s.47
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• pp.569-579
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• 1994

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 phenotype 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-hydroxyebrisoquine(4-HDBR) in a aliquot of an eight hour urine sample, after 10mg DBR test dose administration. Analysis was performed on a capillary gas chromatograph fitted with electron capture detector. The results were as follows; 1 Geometric mean of 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 phenotype 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.

• 대한임상약리학회:학술대회논문집
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• 1992.11a
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• pp.40-40
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• 1992

• Journal of Pharmaceutical Investigation
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• v.15 no.1
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• pp.22-31
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• 1985

The influence of some sympathetic blocking agents on pressor actions of norepinephrine and angiotensin was investigated in rabbits. 1. Phentolamine, sympathetic ${\alpha}-blocking$ agent, blocked the pressor action of norepinephrine, but did not affect the pressor action of angiotensin 2. Chlorisondamine, autonomic ganglionic blocking agent, potentiated the both actions of norepinephrine and angiotensin. 3. Guanethidine, bethanidine and debrisoquine, sympathetic neuronal blocking agents, potentiated the action of norepinephrine, while diminished that of angiotensin. 4. Reserpine, norepinephrine depleting agent, increased the pressor response of norepinephrine, but did not influence the pressor action of angiotensin.

• YAKHAK HOEJI
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• v.36 no.4
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• pp.379-389
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• 1992

In order to investigate the effect of nifedipine, $Ca^{+2}$ channel antagoninst, on the action of some drugs participating in blood pressure, this experiment was peformed in rabbits. Nifedipine decreased the pressor actions of norepinephrine, angiotensin and carotid artery clamping, but did not affect the pressor actions of tyramine and depressor actions of acetylcholine and pilocarpine. Nifedipine inhibited the potentiated pressor action of norepinephrine and angiotensin, but did not influence the potentiated pressor action of tyramine in rabbits pretreated with chlorisondamine, ganglionic blocking agent. Nifedipine weakened the potentiated pressor action of norepinephrine, did not affect the pressor action of angiotensin and the potentiated pressor action of tyramine in rabbits pretreated with debrisoquine, sympathetic neuronal blocking agent.

• Korean Journal of Biological Psychiatry
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• v.7 no.2
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• pp.140-146
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• 2000

P450 CYP2D6 enzyme(=debrisoquine hydroxylase) is known to metabolize many neuroleptics and some genetic polymorphisms in the CYP2D6 gene were reported to be associated with tardive dyskinesia(TD). We investigeted the association of two genetic polymorphisms in the CYP2D6 gene, $CYP2D6^*4$ and $CYP2D6^*10$, with TD in Korean schizophrenic subjects. Subjects consisted of 71 Korean schizophrenics and TD was evaluated using the Abnormal Involuntary Movement Scale (AIMS). There were no statistically significant differences in the demographic variables of age, male to female percentage and the current antipsychotic(CPZ equivalent) dose between the group with TD and the group without TD. But the duration of antipsychotic drug exposure was significantly higher in the group without TD(p=0.000, by independent t-test). The mean AIMS score in the group with TD was $11.2{\pm}6.6$(S.D.). Genotypings for the presence of $CYP2D6^*4$ and $CYP2D6^*10$ were done using PCR amplifications and endonuclease digestions. There were no statistically significant genotypic and alleleic associations between TD and $CYP2D6^*4$(by chisquare tests), and between TD and $CYP2D6^*10$(by chi-square tests). These results indicate that the $CYP2D6^*4$ and $CYP2D6^*10$ polymorphisms have no significant roles in the causation of TD.