• The Korean Journal of Physiology and Pharmacology
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• v.9 no.4
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• pp.223-230
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• 2005

The purpose of the present study was to examine the effect of naltrexone, an opioid antagonist, on secretion of catecholamines (CA) evoked by cholinergic nicotinic stimulation and membrane-depolarization from the isolated perfused rat adrenal gland and to establish the mechanism of its action. Naltrexone $(3{\times}10^{-6}M)$ perfused into an adrenal vein for 60 min produced time-dependent inhibition in CA secretory responses evoked by ACh $(5.32{\times}10^{-3}M)$ , high $K^+$ $(5.6{\times}10^{-2}M)$ , DMPP ($10^{-4}$ M) and McN-A-343 $(10^{-4}M)$ . Naltrexone itself did also fail to affect basal CA output. In adrenal glands loaded with naltrexone $(3{\times}10^{-6}M)$ , the CA secretory responses evoked by Bay-K-8644, an activator of L-type $Ca^{2+}$ channels and cyclopiazonic acid, an inhibitor of cytoplasmic $Ca^{2+}-ATPase$, were also inhibited. However, in the presence of met-enkephalin $(5{\times}10^{-6}M)$ , a well-known opioid agonist, the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly inhibited. Collectively, these experimental results demonstrate that naltrexone inhibits greatly CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as that by membrane depolarization. It seems that this inhibitory effect of naltrexone does not involve opioid receptors, but might be mediated by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of $Ca^{2+}$ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself.

• Archives of Obesity and Metabolism
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• v.1 no.2
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• pp.83-88
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• 2022

Obesity increases the risk of developing metabolic diseases such as hypertension, type 2 diabetes, hyperlipidemia, and cardiovascular diseases, as well as some cancers. To prevent the occurrence of these diseases and death, it is essential to manage obesity. Though there are several treatments for obesity, lifestyle interventions, such as diet and exercise, and drug therapy are most widely used in clinical practice. Among the anti-obesity drugs available, the weight loss effect of naltrexone/bupropion has been well-proven. We present a case study in which naltrexone/bupropion, a glucagon-like peptide-1 agonist, and a sodium-glucose transporter 2 inhibitor showed significant weight loss and improved metabolic parameters. Additionally, the management of type 2 diabetes and hypertension, which are common diseases in patients with obesity, was also included.

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.193-203
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• 2003

Objectives : In this study, we investigated the effect and pathway of contralateral heterotropic electroacupuncture (EA) on pain induced by fonualin in rats. Methods : Acu-points in the right forepaws, HT 7 and PC 7 were stimulated with 3~4mA, 2ms, and 10Hz after 5% formalin (50ul) s.c. injection to the left hind paw. In addition, it was investigated whether the dorsolateral funiculus (DLF), known to be related the descending inhibition, mediates analgesic effects of the contralateral heterotropic EA or whether administration of naltrexone, an opioid antagonist, blocks the effect of EA. Results : The results showed that contralateral heterotropic electroacupuncture (EA) inhibited late phase (63.311.7%) of pain induced by fonualin in the behavioral test, but sham-EA had little effect on pain behavior (85.616.8%) and no analgesic effects after transection of the dorsolateral funiculus (95.718.7%). The pretreatment of naltrexone (10mg/kg, i.p.) could not inhibit the analgesic effects of EA on formalin-induced pain behavior (70.713.1%). Also,EA suppressed formalin injection induced expression of cFos like protein (cFL) in the dorsal homo but not sham-EA. Suppressed expressions of cFL in the spinal cord were eliminated after transection of the ipsilateral dorsolateral funiculus at T10-11 leve1s. However, pretreatment of naltrexone could not prevent the suppressive expressions of cFL at the spinal cord. Conclusions : These results suggest that the analgesic effect of contralateral heterotropic electroacupuncture may be modulated through the dorsolateral funiculus constituting the descending inhibition.

• Journal of Life Science
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• v.19 no.4
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• pp.532-537
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• 2009

Previous studies reported that the N-methyl-D-aspartate (NMDA) receptor is related to alcohol dependence in terms of developing withdrawal or tolerance, however, it is controversial whether NMDA receptor antagonists are effective in preventing relapse in alcohol-dependent patients or not. The purpose of this study was to investigate the effect of memantine, an NMDA receptor antagonist, on alcohol intake in C57BL/6 mice, which prefer drinking hereditarily. Using limited access procedures in C57BL/6 mice in the state of alcohol dependence, vehicle, naltrexone 1.0 mg/kg or, memantine 5, 25, or 50 mg/kg i.p. was administered respectively for twelve days. Medication effects on 2-hours alcohol, 22-hour water, and 24-hour food intake and body weight were studied. Using repeated measure ANOVA, the naltrexone 1 mg/kg, memantine 5, 25, or 50 mg/kg, and vehicle groups showed significant medication by day interaction (naltrexone, df=4, F=11.827, p<0.01, memantine 5 mg/kg, df=4, F=7.999, p<0.01; memantine 25 mg/kg, df=4, F=6.199, p<0.05; memantine 50 mg/kg, df=4, F=10.522, p<0.01) in 2-hour alcohol intake. In 3 memantine groups, there was no significant medication by day interaction with the vehicle group in 22-hour water intake, 24-hour food intake, or body weight. The naltrexone and vehicle groups showed significant medication by day interaction in body weight, but not in 22-hour water or 24-hour food intake. From these results, it is suggested that memantine treatment can affect alcohol intake in mice. Therefore, it is possible that a pure NMDA receptor antagonist is effective in preventing relapse in alcohol-dependent patients.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.10 no.2
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• pp.244-251
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• 1999

Self-injurious behavior is often showed in mental retardation, especially in autism. Self-injurious behavior has been regarded as a symptom cluster rather than a disease but it is an emergent clinical situation that can directly affect mortality. This case is about a refractory autistic patient who showed a self-injurious behavior of hitting the head repetitively. He was hospitalized and was treated by pharmacotherapy and behavior therapy and for this reason this clinical experience is reported with literature review. The patient is a 7-year old boy who was ward admitted from 1999 April 20 till July 10 into OO hospital OO ward because of self-injurious behavior. During the 12 weeks he had admission treatment. As for the pharmacotherapy, haloperidol was dosed up from 0.5mg to 1.0mg from the 4th week and combination drug therapy was done during the admission with naltrexone 25-50mg. As for the behavioral therapy, Differential Reinforcement of Other behavior was used and regular play therapy was done. To remove the physical restraint, headgear and hard sleeve was used. Currently, OPD follow up treatment is being done and haloperidol 0.5mg and naltrexone 50mg is maintained. The patient’s mother is educated and play therapy is done an hour daily at home. When the patient was released form the hospital, self-injurious behavior was decreased more than the moderate state and remission state is still being maintained at the outpatient clinic.

• Journal of Life Science
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• v.17 no.11
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• pp.1576-1581
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• 2007

Dopamine reward pathway projecting from ventral tegmental area to nucleus accumbens is well known as playing an important role in alcohol dependence. It is supposed that this dopamine pathway is modulated by $5-HT_3$ nervous system, and it was reported that ondansetron (OND), $5-HT_3$ receptor antagonist, reduced drinking amount and increased abstinence rate in alcohol-dependent patients. The purpose of this study is to investigate the effect of combination of OND and naltrexone (NTX), non-specific opioid receptor antagonist, on alcohol intake in C57BL/6 mice. In 40 C57BL/6 mice in the state of alcohol dependence, vehicle, while OND 0.01 mg/kg, or NTX 1.0 mg/kg administrated respectively, or OND 0.01 mg/kg and NTX 1.0 mg/kg administrated simultaneously for ten days, medication effects on 2-hr alcohol, 22-hr water, 24-hr food intake and body weight were studied. When vehicle group was compared with 3 medication groups respectively, using a repeated measure ANOVA, NTX alone and vehicle groups showed a significant medication by time interaction (p=0.042) in 2-hr alcohol intake, but in the other 2 groups, OND and NTX combination group and OND alone group, there was no significant interaction with vehicle group in 2-hr alcohol intake. From these results, it is suggested that there is no effect on alcohol intake in mice treating with OND, and naltrexone#s suppression effect on alcohol intake in mice is attenuated when treating with OND and NTX simultaneously. It is supposed that a further study looking at the interactions of serotonin, dopamine and opioid nerves systems will be needed.

• Biomolecules & Therapeutics
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• v.18 no.3
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• pp.316-320
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• 2010

Pruritus is one of major symptoms in atopic dermatis. The pathophysiological mechanism of pruritus is unclear. The search for pruritogen is important in elucidating the pathophysiological mechanism of pruritus in atopic dermatitis. Glucosylsphingosine (Gsp) is upregulated in the strateum corneum of atopic dermatitis patients. We investigated to determine whether Gsp induces itch-scratch responses (ISRs) in mice. Intradermal administration of Gsp induces ISRs. Gsp dose-dependently induced scratching response at 50-500 nmol/site range. Pretreatment with naltrexone, an opioid $\mu$ receptor antagonist, and capsaicin, a TrpV1 receptor agonist, inhibited Gsp-induced ISRs. Additionally, Gsp-induced ISRs were also suppressed by cyproheptadine, an antagonist of serotonin receptor. These findings suggest that Gsp-induced scratching might be at least partly mediated by capsaicin-sensitive primary afferents, and the opioids receptor systems might be involved in transmission of itch signaling in the central nervous system. Furthermore, our findings suggest that Gsp-induced ISRs may be attributable to the serotonin-mediated pathways and Gsp is not any more one of byproducts of abnormal skin barrier but can lead to induce pruritus, one of typical symptoms of atopic dermatitis.

• Korean Journal of Veterinary Research
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• v.39 no.1
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• pp.34-44
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• 1999

Ischemic damage in the selectively vulnerable populations of neurons is thought to be caused by an abnormal accumulation of intracellular calcium. It has been reported that the neurons, expressing specific calcium binding proteins, might effectively control intracellular calcium concentrations because of a high capacity to buffer intracellular calcium in the brain ischemic condition. It is uncertain that parvalbumin, one of the calcium binding proteins, can protect the neurons from the cerebral ischemic damage. Recently, treatment of kappa opioid agonists increased survival rate, improved neurological function, and decreased tissue damage under the cerebral ischemic condition. Many evidences indicate that these therapeutic effects might result from regulation of calcium concentration. This study was designed to analyze the changes of number in parvalbumin-positive neurons after cerebral ischemic damage according to timepoints after cerebral ischemic induction. In addition, we evaluated the effect of GR89696 (kappa opioid agonist) or naltrexone(non selective opioid antagonist) on the changes of number in parvalbumin expressing neurons under ischemic condition. Cerebral ischemia was induced by occluding the common carotid artery of experimental animals. The hippocampal areas were morphometrically analyzed at different time point after ischemic induction(1, 3, 5 days) by using immuno-histochemical technique and imaging analysis system. The number of parvalbumin-positive neurons in hippocampus was significantly reduced at 1 day after ischemia(p<0.05). Furthermore, the number of parvalbumin-immunoreactive neurons was dramatically reduced at 3 and 5 days after cerebral ischemic induction(p<0.05) as compared to 1 day group after ischemia, as well as sham control group. Significant reduction of parvalbumin positive neurons in CA1 region of hippocampus was observed at 1 day after cerebral ischemic induction. However, significant loss of MAP2 immunoreactivity was observed at 3 day after cerebral ischemia. The loss of parvalbumin-positive neurons and MAP2 immunoreactivity in CA1 region was prevented by pre-administration of GR89696 compared to that of saline-treated ischemic group. Furthermore, protective effect of GR89696 partially reversed by pre-treatment of naltrexone. These data indicate that parvalbumin-positive neurons more sensitively responded to cerebral ischemic damage than MAP2 protein. Moreover, this loss of parvalbumin-positive neurons was effectively prevented by the pretreatment of kappa opioid agonist. It was also suggested that the changes of number in parvalbumin-positive neurons could be used as the specific marker to analyze the degree of ischemic neuronal damage.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.4 no.1
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• pp.27-38
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• 1993

Pervasive developmental disorder is one of the most severe clinical disorder in child psychiatry and is associated with deviancies in multiple areas of development. Medication does not cure pervasive developmental disorder and its effectiveness is generally nonspecific. But psychopharmacological treatment can be important for some children with pervasive developmental disorder and can make many young autistics more amenable to behavior modification and education. Haloperidol, the most widely studied antipsychotics, was statistically and clinically superior to placebo, and furthermore, was known to facilitate the positive functioning such as, discrimination learning and imitative communication, without side effects. However, administration of haloperidol is associated with drug related dyskinesia, and it warrants the introduction and use of the other novel drugs. Several biochemical studies suggest that subgroups of children with pervasive developmental disorder show hyperserotonemia and increased endogenous opioid level as compared with controls. Psychopharmacological trials were conducted according to these findings(ex : fenfluramine, naltrexone), with mixed results till now. These and another drugs that have been used in children with pervasive developmental disorder and their effectiveness are reviewed.

• Korean Journal of Clinical Pharmacy
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• v.16 no.1
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• pp.69-74
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• 2006

날트렉손은 ${\mu}-opioid$ 수용체에 특이적이고 선택적으로 길항작용을 나타내어 마약이나 마약성 진통제의 강한 의존성 치료에 쓰일 뿐만 아니라, 알코올 의존성 치료에도 쓰이는 약물이다. 본 연구는 날트렉손 제제인 레비아 정 (50 mg tablet, 제일약품) 을 대조약으로 하여 시험약인 명인 제약의 트락손 50 mg정의 생물학적 동등성 평가를 하기 위해 22명의 건강한 지원자를 모집하였다. 지원자를 두 군으로 나누어 1정씩 투여하였고 $2{\times}2$ 교차시험을 실시하였다. 날트렉손의 혈장 중의 농도를 정량하기 위하여 발리데이션된 LC/MS/MS를 사용하였다. 채혈 시간은 투약 전 및 투약 후 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12 시간에 걸쳐 시행하였다. 생물학적 동등성을 판정하기 위한 파라미터로 12시간까지의 혈장 중 농도 곡선 하 면적$(AUC_{12hr})$과 최고 혈중 농도 $(C_{max})$를 사용하였다. $AUC_{12hr}$의 평균은 $43.45ng{\cdot}hr/ml$ (시험약)과 $43.31ng{\cdot}hr/ml$ (대조약) 으로 관찰되었고, $C_{max}$의 경우 각각 12.01 ng/m1 (시험약)과 12.27 ng/ml (대조약)으로 관찰되었다. $AUC_{12hr}$의 경우 로그변환 한 평균치 차의 90%의 신뢰구간이 log0.95-log1.07이었고, $C_{max}$의 경우 log0.87-log1.14로 계산되어 두 항목 모두 log0.8-log1.25이어야 한다는 식품의약품 안전청과 FDA의 기준을 모두 만족시켰다. 이상의 결과를 종합하면 시험약 트락손 정 50mg 은 대조약 레비아 정 50 mg에 대하여 생물학적으로 동등한 것으로 판정되었다.