• Archives of Pharmacal Research
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• 제14권4호
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• pp.290-294
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• 1991

For the determination of peripheral COMT activity, we synthesized $[2-^{14}C]-3',4'-dihydroxyacetophenone([^{14}C]-DHAP)$, a model substrate closely related to catecholamines, which cannot be attacked by monoamine oxidase. After i.v.-injection of $[^{14}C]-DHAP$ in living animals, only 3',4'-dihydroxy-acetophenone (3',4'-DHAP) and 3'-methoxy-4'-hydroxyacetophenone (3'-MHAP) were detected in blood by thin layer radio chromatography. It could be speculated that 3',4'-DHAP was primarily O-methylated by COMT, followed by subsequent conjugations. The concentration of 3',4'-DHAP, a substrate for COMT, in blood at 5 min after injection of $[^{14}C]-DHAP$, were similar in all animals. The rate of 3'-MHAP formation can be therefore used as an indicator for peripheral COMT activity. The velocity of methylation in 15 min after i.v.-administration of $[^{14}C]-DHAP$ was $0.28\;{\mu}g/ml{\cdot}min$. From these results, 3',4'-DHAP was shown to be used as an appropriate substrate to determine the COMT activity in vivo.

• 대한약리학회지
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• 제26권1호
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• pp.67-76
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• 1990

웅성-마우스의 고환을 diethyl ether 마취하에서 제거하고, 수종의 steroid 홀몬을 각각 매일 1회씩 4일간 피하주사하여, 간 및 소장의 polyamine 함량과 소장의 diamine oxidase (DAO) 활성도에 미치는 그들의 영향을 검색하였다. 1. Hydrocortisone succinate 50 mg/kg (HC) 및 dehydroepiandrosterone 250 mg/kg (DHEA)에 의하여, 소장의 putrescine (PT)은 유의하게 증가되었으나, spermidine (SD) 및 spermine (SM)은 별 영향을 받지 않았고, 간의 SD은 다소 증가되고, SM은 다소 감소 되었으나, PT은 별 변동을 보이지 않았다. 2. Estradiol cypionate 5 mg/kg (E2)에 의하여, 간의 PT은 현저히 증가되었으나, 소장의 PT은 다소 증가되었고, 그외 소장 및 간의 SD와 SM의 변동은 보이지 않았다. Testosterone cypionate 5 mg/kg (TS)에 의하여는 간의 SD이 다소 감소되었을 뿐 별 변동이 없었다. 3. 소장의 DAO 활성도는 HC에 의하여 현저히 감소되었으나, E2 및 TS에 의하여는 유의하게 증가되었고, DHEA에 의하여는 별 영향을 받지않았다. 그러나 간의 monoamine oxidase 활성도는 HC, E2, DHEA, 및 TS에 의하여 영향을 받지 않았다. 4. Aminoguanidine 25 mg/kg로 소장의 DAO 활성도가 현저히 감소되었으나, 간 MAO 활성도는 영향을 받지 않았고, 소장의 PT 및 SD은 유의하게 증가되었으나, 간의 polyamine은 별 변동을 보이지 않았다. 이상의 결과로 미루어 볼때, 간 및 소장의 polyamine 대사-특히 PT 함량의 변동이 각각 E2 및 HC에 의하여 특이적으로 조절되는 바, E2에 의한 간 PT 함량의 증가는 주로 생성촉진 작용에 연유되며, HC에 의한 소장 PT 함량의 증가는 주로 polyamine의 이화성 대사를 억제함에 기인될 수 있는 것으로 사료된다.

• 한국임상약학회지
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• 제25권2호
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• pp.120-129
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• 2015

Objectives: Drug utilization review program in Korea has provided 'drug combinations to avoid (DCA)' alerts to physicians and pharmacists to prevent potential adverse drug events or inappropriate drug use. Seven hundred and six DCA pairs have been announced officially by the Ministry of Food and Drug Safety (MFDS) by March, 2015. Some DCA pairs could be grouped based on the drug interaction mechanism and its consequences. This study aimed to investigate the drug-drug interaction (DDI) pairs, which may be potential DCAs, generated by the drug class-drug class interaction method. Methods: Eleven additive/synergistic and one antagonistic drug class-drug class interaction groups were identified. By combining drugs of two interacting drug class groups, numerous DDI pairs were made. The status and severity of DDI pairs were examined using Lexicomp and Micromedex. Also, the DCA listing rate was calculated. Results: Among 258 DDI pairs generated by the drug class-drug class interaction method, only 142 pairs were identified as official DCA pairs by the MFDS. One hundred and four pairs were identified as potential DCA pairs to be listed. QT prolonging agents-QT prolonging agents, triptans-ergot alkaloids, tricyclic antidepressants-monoamine oxidase inhibitors, and dopamine agonists-dopamine antagonists were identified as drug class-drug class interaction groups which have less than 50 % DCA listing rate. Conclusion: To improve the clinicians' adaptability to DCA alerts, the list of DCA pairs needs to be continuously updated.

• The Korean Journal of Physiology and Pharmacology
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• 제6권1호
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• pp.9-14
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• 2002

In the present study, we used the microdialysis technique combined with high performance liquid chromatography (HPLC) and electrochemical detection to measure the extracellular levels of norepinephrine (NE) in the posterior hypothalamus in vivo, and to examine the effects of various drugs, affecting central noradrenergic transmission, on the extracellular concentration of NE in the posterior hypothalamus. Microdialysis probes were implanted stereotaxically into the posterior hypothalamus (coordinates: posterior 4.3 mm, lateral 0.5 mm, ventral 8 mm, relative to bregma and the brain surface, respectively) of rats, and dialysate collection began 2 hr after the implantation. The baseline level of monoamines in the dialysates were determined to be: NE $0.17{\pm}0.01,$ 3,4-dihydroxyphenylacetic acid (DOPAC) $0.94{\pm}0.07,$ homovanillic acid (HVA) $0.57{\pm}0.05$ pmol/sample (n=8). When the posterior hypothalamus was perfused with 90 mM potassium, maximum 555% increase of NE output was observed. Concomitantly, this treatment significantly decreased the output of DOPAC and HVA by 35% and 28%, respectively. Local application of imipramine $(50\;{\mu}M)$ enhanced the level of NE in the posterior hypothalamus (maximum 200%) compared to preperfusion control values. But, DOPAC and HVA outputs remained unchanged. Pargyline, an irreversible monoamine oxidase inhibitor, i.p. administered at a dose of 75 mg/kg, increased NE output (maximum 165%), while decreased DOPAC and HVA outputs (maximum 13 and 12%, respectively). These results indicate that NE in dialysate from the rat posterior hypothalamus were neuronal origin, and that manipulations which profoundly affected the levels of extracellular neurotransmitter had also effects on metabolite levels.

• The Korean Journal of Pain
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• 제29권3호
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• pp.153-157
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• 2016

Tapentadol is a novel oral analgesic with a dual mode of action as an agonist of the ${\mu}$-opioid receptor (MOR), and as a norepinephrine reuptake inhibitor (NRI) all in a single molecule. Immediate release (IR) tapentadol shows its analgesic effect quickly, at around 30 minutes. Its MOR agonistic action produces acute nociceptive pain relief; its role as an NRI brings about chronic neuropathic pain relief. Absorption is rapid, with a mean maximal serum concentration at 1.25-1.5 h after oral intake. It is present primarily in the form of conjugated metabolites after glucuronidation, and excretes rapidly and completely via the kidneys. The most common adverse reactions are nausea, dizziness, vomiting, and somnolence. Constipation is more common in use of the ER formulation. Precautions against concomitant use of central nervous system depressants, including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol, or use of tapentadol within 14 days of the cessation of monoamine oxidase inhibitors, are advised. The safety and efficacy have not been established for use during pregnancy, labor, and delivery, or for nursing mothers, pediatric patients less than 18 years of age, and cases of severe renal impairment and severe hepatic impairment. The major concerns for tapentadol are abuse, addiction, seeking behavior, withdrawal, and physical dependence. The presumed problem for use of tapentadol is to control the ratio of MOR agonist and NRI. In conclusion, tapentadol produces both nociceptive and neuropathic pain relief, but with worries about abuse and dependence.

• 약학회지
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• 제49권4호
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• pp.355-364
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• 2005

A neurotoxin, 6-hydroxydopamine (6-OHDA) has long been used to form a Parkinson's disease (PD) model by inducing the lesion in catecholaminergic pathways, particularly the nigrostriatal dopamine (DA) pathway. Whereas l-deprenyl, a selective inhibitor of monoamine oxidase (MAO) type B, is now widely used in the treatment of PD, the precise action mechanism of the drug remains elusive. In this study, we investigated whether l-deprenyl shows protective effect against the DA depletion induced by 6-OHDA in rat brain, and against 6-OHDA-induced neurotoxicity and oxidative stress in catecholaminergic neuroblastoma SH-SY5Y cells that are known to lack MAO-B activity. Pretreatment of l-deprenyl significantly enhanced the striatal DA, 3,4-dihydroxyphenylacetic acid, homovanilic acid, and 3-methoxytyramine levels compared to the untreated 6-OHDA-lesioned rat, indicating that l-deprenyl pretreatment prevents 6-OHDA-induced depletion of not only striatal dopamine but also its metabolites. Treatment of 6-OHDA for 24hrs decreased the cell viability and increase the generation of ROS in dose-dependent manners. We further investigated whether caspase activity is involved in the action of l-deprenyl. Treatment of l-deprenyl $(0.1\~100{\mu}M)$ did not produce any changes in 6-OHDA-induced cleavage of poly (ADP-ridose) polymerase in SH-SY5Y cells. Our results suggest that the neuroprotective effect of l-deprenyl against 6-OHDA is due to its increased scavenger activity, but independent of inhibition of MAO-B or caspase-3 activation.

• 생물정신의학
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• 제23권3호
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• pp.108-115
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• 2016

Aggression and aggressive behaviors, often explained as harmful social interaction with the intention of hurting or inflicting damage upon another, have been considered as an adaptive mechanism from the evolutionary psychological point of view. However, various studies on aggression and aggressive behaviors have been done with psychopathological approach as the extreme aggressive behaviors may harm themselves and others at the same time. Recently, researchers have attempted to explain aggression in terms of neurobiological substrates rather than based on traditional psychopathological and/or behavioral concept. In this regard, there have been findings of differences in neurotransmitters and their receptors, and genetic polymorphisms. In this review article, we provide a brief overview of the literature about seven most frequently reported neurotransmitters including neurohormones (serotonin, norepinephrine, dopamine, gamma-aminobutyric acid, nitric oxide, oxytocin and vasopressin) and an associated enzyme (monoamine oxidase A), which are known to be related with aggression and aggressive behaviors.

• 한국축산식품학회지
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• 제40권2호
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• pp.183-196
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• 2020

The protective effect of pig skin gelatin water extracts (PSW) and the low molecular weight hydrolysates of PSW generated via enzymatic hydrolysis with Flavourzyme® 1000L (LPSW) against scopolamine-induced impairment of cognitive function in mice was determined. Seventy male ICR mice weighing 20-25 g were randomly assigned to seven groups: Control (CON); scopolamine (SCO, 1 mg/kg B.W., intraperitoneally (i.p.); tetrahydroaminoacridine 10 [THA 10, tacrine; 10 mg/kg B.W. per oral (p.o.) with SCO (i.p.)]; PSW 10 (10 mg/kg B.W. (p.o.) with SCO (i.p.); PSW 40 (40 mg/kg B.W. (p.o.) with SCO (i.p.); LPSW 100 (100 mg/kg B.W. (p.o.) with SCO (i.p.); LPSW 400 (400 mg/kg B.W. (p.o.) with SCO (i.p.). All treatment groups, except CON, received scopolamine on the day of the experiment. The oxygen radical absorbance capacity of LPSW 400 at 1 mg/mL was 154.14 μM Trolox equivalent. Administration of PSW and LPSW for 15 weeks did not significantly affect on physical performance of mice. LPSW 400 significantly increased spontaneous alternation, reaching the level observed for THA and CON. The latency time of animals receiving LPSW 400 was higher than that of mice treated with SCO alone in the passive avoidance test, whereas it was shorter in the water maze test. LPSW 400 increased acetylcholine (ACh) content and decreased ACh esterase activity (p<0.05). LPSW 100 and LPSW 400 reduced monoamine oxidase-B activity. These results indicated that LPSW at 400 mg/kg B.W. is a potentially strong antioxidant and contains novel components for the functional food industry.

• 동의신경정신과학회지
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• 제17권3호
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• pp.21-43
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• 2006

This study was designed to assess Effects of jingansikpungtanggagam-bang on Central Nerve System. Method : jingansikpungtanggagam-bang, a Korean traditional prescription, was evaluated for its anticonvulsant effect, hypnotic activity, analgesic action, anxiolytic effect, memory enhancement, and MAO inhibitory activity and detennined the content of neurotransmitter in brain by HPLC method. Result : 1. The extract increased potently anticonvulsant effect at 1g/kg by 5.6-fold extention of onset time against control group. 2. The extract increased hvrmsis at 500mg/kg by over twofold length of sleeping time compared to control. 3. The extract showed a significant analgesic effect with 86.0% inhibition on writhing frequency at 500mg/kg by phenylquinone-induced writhing test. 4. The extract inhibited dose-dependently the activity of monoamine oxidase in vitro. 5. This prescription increased the brain levels of serotonin and 5-hydroxyindoleacetic acid by 3.3% and 1.4%, respectively. 6. the extract exhibited the anxiolytic effect with 21.3% decrease of the immobility duration against control group. 7. the extract enhanced memory recovery on scopolamine-induced impairment of passive avoidance performance at 1g/kg pretreatment with 20.2% increase of latency time. Conclusion : The result sugguest that jiugansikpungtanggagam-bang can be used effectively as a sedative prescription in Korean traditional medicine.

• 약학회지
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• 제43권1호
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• pp.33-41
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• 1999

Whereas as selective inhibitor of monoamine oxidase type B, ${\ell}-deprenyl$ (selegiline), is now widely used in the treatment of Parkinson's disease, the precise action mechanism of the drug remains elusive. In this study, to investigate protective effect of ${\ell}-deprenyl$ against the dopamine depletion induced by 6-hydroxydopamine (6-OHDA), the changes in tissue contents of dopamine, serotonine (5-HT) and their metabolites by ${\ell}-deprenyl$ were examined in intact and 6-OHDA-lesioned rat brain. In intact rats, a single intraperitoneal (i.p.) administration of ${\ell}-deprenyl$ showed a no change in striatal dopamine and its metabolites at low concentrations (0.25 and 1 mg/kg), but significantly inhibited dopamine metabolism at a higher concentration (10 mg/kg). The repeated administration of ${\ell}-deprenyl$ (0.25 and 1 mg/kg, i.p., for 21 consecutive days) reduced the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in dose-dependent manners without changes in dopamine content. Bilateral intracerebroventricular (i.c.v) infusion of 6-OHDA ($100{\;}\mu\textrm{g}/10{\;}{\mu}{\ell}/hemisphere$) depleted dopamine in striatum and septum by 81% and 90% respectively. When rats were pretreated with ${\ell}-deprenyl$ before 6-OHDA administration, the striatal and septal dopamine levels were significantly increased by about 3.0-fold and 3.4-fold, respectively, compared to the untreated 6-OHDA-lesioned rat. Pretreatment of ${\ell}-deprenyl$ also significantly enhanced the dopmaine metabolites, DOPAC, HVA and 3-methoxytyramine, in the striatum, and DOPAC in the septum. These results indicate that a ${\ell}-deprenyl$ pretreatment prevents 6-OHDA-induced depletion of striatal dopamine and its metabolites.