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1.
Article in Korean | WPRIM | ID: wpr-765212

ABSTRACT

Clinical studies published over the past two decades have consistently demonstrated the therapeutic efficacy and safety of anti-craving medications. To use anti-craving agents more effectively in clinical settings, it is important to set clear treatment goals. Because alcoholic patients have lost control of drinking alcohol, it is recommended to set ‘abstinence’ as a goal rather than ‘controlled drinking’. Indeed, the therapeutic effects of anti-craving medication are higher when abstinence is set as the target. On the other hand, if abstinence is the sole criterion, it is difficult to elicit the motivation of a patient who lacks motivation in clinical practice. In the case of patients who have not yet gained insight, the initial goal might be set to gradually reduce the amount of alcohol consumed and prevent at-risk heavy drinking. Even in this case, anti-craving can help clinically. To increase the effectiveness of anti-craving medications, it is best to start at least four to seven days after the patient has stopped drinking. If the patient has alcohol withdrawal symptoms, they should be treated first.


Subject(s)
Alcoholics , Craving , Drinking , Hand , Humans , Motivation , Naltrexone , Substance Withdrawal Syndrome , Therapeutic Uses
2.
Article in English | WPRIM | ID: wpr-763521

ABSTRACT

Naltrexone is a competitive antagonist of μ, δ, and κ opioid receptors. Naltrexone has been investigated for use an as anti-obesity agent in both the general population and in patients with severe mental illness, including schizophrenia. In patients with schizophrenia, however, potential psychotic symptoms due to adverse effects of naltrexone have not been investigated. Our case study, a relevant case report, and some related articles suggest that naltrexone might be associated with the emergence of visual hallucinations, which clinicians should be aware of.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Hallucinations , Humans , Naltrexone , Narcotic Antagonists , Receptors, Opioid , Schizophrenia
3.
Article in Korean | WPRIM | ID: wpr-760321

ABSTRACT

OBJECTIVES: The current study covers a secondary revision of the guidelines for the pharmacotherapy of schizophrenia issued by the Korean Medication Algorithm for Schizophrenia (KMAP-SCZ) 2001, specifically for co-existing symptoms and antipsychotics-related side-effects in schizophrenia patients. METHODS: An expert consensus regarding the strategies of pharmacotherapy for positive symptoms of schizophrenia, co-existing symptoms of schizophrenia, and side-effect of antipsychotics in patients with schizophrenia was retrieved by responses obtained using a 30-item questionnaire. RESULTS: For the co-existing symptoms, agitation could be treated with oral or intramuscular injection of benzodiazepine or antipsychotics; depressive symptoms with atypical antipsychotics and adjunctive use of antidepressant; obsessive-compulsive symptoms with selective serotonin reuptake inhibitors and antipsychotics other than clozapine and olanzapine; negative symptoms with atypical antipsychotics or antidepressants; higher risk of suicide with clozapine; comorbid substance abuse with use of naltrexone or bupropion/ varenicline, respectively. For the antipsychotics-related side effects, anticholinergics (extrapyramidal symptom), propranolol and benzodiazepine (akathisia), topiramate or metformin (weight gain), change of antipsychotics to aripiprazole (hyperprolactinemia and prolonged QTc) or clozapine (tardive dyskinesia) could be used. CONCLUSION: Updated pharmacotherapy strategies for co-existing symptoms and antipsychotics-related side effects in schizophrenia patients as presented in KMAP-SCZ 2019 could help effective clinical decision making of psychiatrists as a preferable option.


Subject(s)
Antidepressive Agents , Antipsychotic Agents , Aripiprazole , Benzodiazepines , Cholinergic Antagonists , Clinical Decision-Making , Clozapine , Consensus , Depression , Dihydroergotamine , Drug Therapy , Humans , Injections, Intramuscular , Metformin , Naltrexone , Propranolol , Psychiatry , Schizophrenia , Serotonin Uptake Inhibitors , Substance-Related Disorders , Suicide , Varenicline
4.
Article in English | WPRIM | ID: wpr-738872

ABSTRACT

The Korean Ministry of Food and Drug Safety has approved three anti-obesity drugs for long-term management in the past decade. In addition, since 2019, bariatric surgery has been financially supported by National Health Insurance Service in Korea. In this review, the mechanisms of action and the clinical implications of the recently approved anti-obesity drugs, lorcaserin, naltrexone/bupropion, and liraglutide are explained. Lorcaserin stimulates proopiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART) neurons and inhibits neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons, which results in the activation of melanocortin 3/4 receptors. Naltrexone/bupropion stimulates POMC neurons through bupropion; this stimulation is augmented by blocking the autoinhibitory mechanism of POMC with naltrexone. The hypophagic effect of liraglutide is mediated through the direct activation of POMC/CART neurons and the indirect suppression of NPY/AgRP neurons through γ-aminobutyric acid-dependent signaling, with adjunctive suppression of the mesolimbic dopamine reward system. In addition to liraglutide, another glucagon-like peptide-1 receptor agonist, semaglutide, is expected to be added to the list of anti-obesity drugs in the near future. In patients with obesity and high cardiovascular risk, lorcaserin was considered neutral and liraglutide was considered favorable, whereas inconclusive results were obtained for naltrexone/bupropion.


Subject(s)
Anti-Obesity Agents , Bariatric Surgery , Bupropion , Dopamine , Glucagon-Like Peptide-1 Receptor , Humans , Korea , Liraglutide , Naltrexone , National Health Programs , Neurons , Neuropeptide Y , Obesity , Pro-Opiomelanocortin , Reward
5.
Braz. j. med. biol. res ; 51(5): e6714, 2018. tab, graf
Article in English | LILACS | ID: biblio-889083

ABSTRACT

This study aimed to investigate the protective effect of salvinorin A on the cerebral pial artery after forebrain ischemia and explore related mechanisms. Thirty Sprague-Dawley rats received forebrain ischemia for 10 min. The dilation responses of the cerebral pial artery to hypercapnia and hypotension were assessed in rats before and 1 h after ischemia. The ischemia reperfusion (IR) control group received DMSO (1 µL/kg) immediately after ischemia. Two different doses of salvinorin A (10 and 20 µg/kg) were administered following the onset of reperfusion. The 5th, 6th, and 7th groups received salvinorin A (20 µg/kg) and LY294002 (10 µM), L-NAME (10 μM), or norbinaltorphimine (norBIN, 1 μM) after ischemia. The levels of cGMP in the cerebrospinal fluid (CSF) were also measured. The phosphorylation of AKT (p-AKT) was measured in the cerebral cortex by western blot at 24 h post-ischemia. Cell necrosis and apoptosis were examined by hematoxylin-eosin staining (HE) and TUNEL staining, respectively. The motor function of the rats was evaluated at 1, 2, and 5 days post-ischemia. The dilation responses of the cerebral pial artery were significantly impaired after ischemia and were preserved by salvinorin A treatment. In addition, salvinorin A significantly increased the levels of cGMP and p-AKT, suppressed cell necrosis and apoptosis of the cerebral cortex and improved the motor function of the rats. These effects were abolished by LY294002, L-NAME, and norBIN. Salvinorin A preserved cerebral pial artery autoregulation in response to hypercapnia and hypotension via the PI3K/AKT/cGMP pathway.


Subject(s)
Animals , Male , Rats , Cerebral Arteries/drug effects , Brain Ischemia/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Diterpenes, Clerodane/pharmacology , Signal Transduction , Cerebral Arteries/physiopathology , Brain Ischemia/drug therapy , Morpholines/administration & dosage , Chromones/administration & dosage , Rats, Sprague-Dawley , Cyclic GMP/cerebrospinal fluid , Cyclic GMP/metabolism , NG-Nitroarginine Methyl Ester , Diterpenes, Clerodane/antagonists & inhibitors , Disease Models, Animal , Naltrexone/administration & dosage , Naltrexone/analogs & derivatives
6.
Annals of Dermatology ; : 159-163, 2016.
Article in English | WPRIM | ID: wpr-185203

ABSTRACT

BACKGROUND: Severe pruritus is a challenging condition, and it is more difficult to deal with in older patients due to their limitations in taking oral medication because of underlying diseases, possible interaction with concurrent medications, and poor general condition. OBJECTIVE: We evaluated the efficacy and safety of naltrexone (Revia®), an opioid antagonist, in elderly patients with severe pruritus that was not easily controlled with conventional antipruritics. METHODS: Eighteen patients were enrolled, with a mean age of 73 years. They additionally received 50 mg of naltrexone per day for an average of 2 months. RESULTS: Using the visual analogue scale, 13 (72.2%) of 18 patients showed a "much improved" condition, reporting more than a 50% decrease in pruritus intensity. Sixteen (88.9%) showed symptomatic improvement, and only 2 (11.1%) had persistent pruritus. Five patients reported side effects including insomnia, fatigue, constipation, and anorexia. However, reactions were either limited to the first 2 weeks or well managed. CONCLUSION: Naltrexone could be an effective and safe alternative treatment option to control severe pruritus in older patients.


Subject(s)
Aged , Anorexia , Antipruritics , Constipation , Fatigue , Humans , Naltrexone , Pruritus , Sleep Initiation and Maintenance Disorders
7.
Article in Korean | WPRIM | ID: wpr-81043

ABSTRACT

Polydipsia in schizophrenic patients is not uncommon, but a frequently underdiagnosed condition. The etiology of polydipsia remains unclear, and its complications can be life-threatening, while often being difficult to manage it. We report a case of a successfully treated chronic schizophrenic patient with polydipsia. The patient was male, 47-year-old, suffering 27-years of residual schizophrenia who had been consuming more than 10 L of water per day, and is complicated by hyponatremia. He was treated with irbesarten 300 mg and naltrexone 50 mg in the setting of closed ward. He consumed less than 3.5 L of water per day and serum sodium levels seemed to be stable following discharge from the closed ward. We suggest that irbesartan and naltrexone may have beneficial effects for treating polydipsia, and future prospective and well-controlled studies are to be performed.


Subject(s)
Humans , Hyponatremia , Male , Middle Aged , Naltrexone , Polydipsia , Prospective Studies , Schizophrenia , Sodium , Water
8.
Experimental Neurobiology ; : 312-324, 2015.
Article in English | WPRIM | ID: wpr-228169

ABSTRACT

Autism spectrum disorder (ASD) is characterized by persistent deficits within two core symptom domains: social communication and restricted, repetitive behaviors. Although numerous studies have reported psychopharmacological treatment outcomes for the core symptom domains of ASD, there are not enough studies on fundamental treatments based on the etiological pathology of ASD. Studies on candidate medications related to the pathogenesis of ASD, such as naltrexone and secretin, were conducted, but the results were inconclusive. Oxytocin has been identified as having an important role in maternal behavior and attachment, and it has been recognized as a key factor in the social developmental deficit seen in ASD. Genetic studies have also identified associations between ASD and the oxytocin pathway. As ASD has its onset in infancy, parents are willing to try even experimental or unapproved treatments in an effort to avoid missing the critical period for diagnosis and treatment, which can place their child in an irreversible state. While therapeutic application of oxytocin for ASD is in its early stages, we have concluded that oxytocin would be a promising therapeutic substance via a thorough literature review focusing on the following: the relationship between oxytocin and sociality; single nucleotide polymorphisms as a biological marker of ASD; and validity verification of oxytocin treatment in humans. We also reviewed materials related to the mechanism of oxytocin action that may support its potential application in treating ASD.


Subject(s)
Autistic Disorder , Child , Autism Spectrum Disorder , Critical Period, Psychological , Diagnosis , Humans , Maternal Behavior , Naltrexone , Oxytocin , Parents , Pathology , Polymorphism, Single Nucleotide , Secretin , Social Change , Biomarkers
9.
Chinese Journal of Cardiology ; (12): 866-872, 2014.
Article in Chinese | WPRIM | ID: wpr-303812

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effects of κ-opioid receptor agonist U50, 488H on myocardial ischemia and reperfusion injury and related mechanism.</p><p><b>METHODS</b>Rats were randomly divided into sham operation, myocardial ischemia and reperfusion(I/R, 30 min ischemia followed by 120 min reperfusion), and MI/R+U50, 488H (1.5 mg/kg) and I/R+U50, 488H+ selective κ-opioid receptor antagonist Nor-BNI (2 mg/kg, n = 8 each). The infarction size and the incidence of ventricular arrhythmias were observed.Real-time PCR and DAB staining were used to define the myocardium Toll-like receptor 4(TLR4) expression. Myeloperoxidase level, TNF-α induction and the expression of NF-κB were also examined in rats.</p><p><b>RESULTS</b>After I/R, the expressions of myocardial TLR4 and NF-κB increased significantly both in ischemia area and area at risk. Compared with I/R, κ-opioid receptor stimulation with U50, 488H significantly attenuated the expressions of TLR4 and NF-κB and reduced myeloperoxidase (MPO) levels, myocardial TNF-α production, myocardial infarct sizes and the incidence of ventricular arrhythmias and arrhythmia score (2.9 ± 0.7 vs. 4.4 ± 0.9, P < 0.05) , above effects of U50, 488H were partly abolished by co-treatment with Nor-BNI.</p><p><b>CONCLUSION</b>These data provide evidence for the first time that κ-opioid receptor stimulation could attenuate myocardial I/R injury via downregulating TLR4/NF-κB signaling in rats.</p>


Subject(s)
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer , Pharmacology , Animals , Arrhythmias, Cardiac , Brugada Syndrome , Cardiac Conduction System Disease , Coronary Artery Disease , Down-Regulation , Heart Conduction System , Congenital Abnormalities , Myocardial Infarction , Myocardial Ischemia , Metabolism , Myocardium , NF-kappa B , Naltrexone , Rats , Rats, Sprague-Dawley , Receptors, Opioid, kappa , Physiology , Reperfusion Injury , Signal Transduction , Toll-Like Receptor 4 , Physiology , Tumor Necrosis Factor-alpha
10.
Article in English | WPRIM | ID: wpr-60727

ABSTRACT

The purpose of this study was to investigate the differences in subjective acute effects of alcohol and naltrexone among those who prefer spicy food to varying degrees. Acute biphasic alcohol effects scale (BAES), visual analogue scale for craving (VAS-C), blood alcohol concentration (BAC) and food preference scale were measured in 26 men. Repeated measures ANOVA (2 preference groupsx4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in naltrexone condition (N+) (P<0.001), but not in non-naltrexone condition (N-). Furthermore, repeated measures ANOVA (2 drug groupsx4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in strong preference for spicy food (SP) (P<0.001), but not in lesser preference for spicy food (LP). The paired t-test revealed that significant suppression of the stimulative subscale of BAES was observed at 15 min (P<0.001) and 30 min (P<0.001) after drinking when N+ compared with N- in SP. For those who prefer spicy food, the stimulative effect of acute alcohol administration was suppressed by naltrexone. This result suggests that the effect of naltrexone may vary according to spicy food preference.


Subject(s)
Adult , Alcohol Drinking/adverse effects , Alcoholism/drug therapy , Capsaicin/pharmacology , Food Preferences/drug effects , Humans , Male , Naltrexone/adverse effects , Narcotic Antagonists/adverse effects , Surveys and Questionnaires , Sensory System Agents/pharmacology , Young Adult
11.
Article in English | WPRIM | ID: wpr-86621

ABSTRACT

Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care.


Subject(s)
Alcohol Deterrents/therapeutic use , Alcoholism/economics , Benzodiazepines/therapeutic use , Humans , Naltrexone/therapeutic use , Psychotherapy , Republic of Korea , Taurine/analogs & derivatives
12.
Article in English | WPRIM | ID: wpr-49133

ABSTRACT

BACKGROUND: WIN55212-2 is a synthetic cannabinoid agonist and selective to cannabinoid 1 (CB1) receptors, which are distributed mainly in the central nervous system. Opioid receptors and CB1 receptors have several similarities in terms of their intracellular signal transduction mechanisms, distributions, and pharmacological action. Several studies have therefore sought to describe the functional interactions between opioids and cannabinoids at the cellular and behavioral levels. The present study investigated agonist-stimulated [35S]GTPgammaS binding by WIN55212-2 in rat brain membranes and determined the antagonism by selective opioid antagonists at the level of receptor-ligand interaction and intracellular signal transduction. METHODS: Sprague-Dawley rats (male, n = 20) were euthanized for the preparation of brain membranes. In agonist-stimulated [35S]GTPgammaS binding by WIN55212-2, the values of EC50 and maximum stimulation (% over basal) were determined in the absence or presence of the micro, kappa and delta opioid receptor antagonists naloxone (20 nM), norbinaltorphimine (3 nM), and naltrindole (3 nM), respectively. Ke values for opioid antagonist inhibition in the absence or presence of each opioid receptor antagonist were calculated using the following equation: [nanomolar antagonist] / (dose ratio of EC50 - 1). RESULTS: In WIN55212-2-stimulated [35S]GTPgammaS binding in the rat brain membranes, the values of EC50 and maximum stimulation (% over basal) were 154 +/- 39.5 nM and 27.6 +/- 5.3% over basal, respectively. Addition of selective opioid antagonists did not produce a significant rightward shift in the WIN55212-2 concentration-response curve, and Ke values were not applicable. CONCLUSIONS: Our results suggest that the functional activity of WIN55212-2-stimulated [35S]GTPgammaS binding was not affected by opioid antagonists in the rat brain membranes. Although the exact mechanism remains unclear, our results may partially elucidate their actions.


Subject(s)
Analgesics, Opioid , Animals , Benzoxazines , Brain , Cannabinoids , Central Nervous System , Membranes , Morpholines , Naloxone , Naltrexone , Naphthalenes , Narcotic Antagonists , Rats , Rats, Sprague-Dawley , Receptor, Cannabinoid, CB1 , Receptors, Opioid , Receptors, Opioid, delta , Signal Transduction
13.
Article in Korean | WPRIM | ID: wpr-48392

ABSTRACT

Sexual violence crime causes severe trauma to victim's family as well as the victim, and its aftereffect which is hard to be healed can last for the entire lifetime. And thus plenty of social cost is incurred due to the crime. It has long been reported that paraphilia is associated with sexual offenders and sexual violence. In this study, the previous foreign data on the psychiatric medication used for sexual offender or paraphilia were summarized for the first time in Korea, and the possibility of medication in Korea was examined. As for the drugs used for sexual offender or paraphilia, SSRI was most frequently reported and besides that, tricyclic antidepressant, antipsychotics, antiepileptic drugs, mirtazapine, and naltrexone were reported.


Subject(s)
Anticonvulsants , Antipsychotic Agents , Crime , Criminals , Humans , Korea , Mianserin , Naltrexone , Paraphilic Disorders , Sex Offenses
14.
Yonsei Medical Journal ; : 763-771, 2013.
Article in English | WPRIM | ID: wpr-211909

ABSTRACT

PURPOSE: Nociceptin/orphanin FQ (N/OFQ) as an endogeneous hexadecapeptide is known to exert antinociceptive effects spinally. The aims of this study were to demonstrate the antinociceptive effects of i.t. N/OFQ and to investigate the possible interaction between N/OFQ and endogenous opioid systems using selective opioid receptor antagonists in rat formalin tests. MATERIALS AND METHODS: I.t. N/OFQ was injected in different doses (1-10 nmol) via a lumbar catheter prior to a 50 microL injection of 5% formalin into the right hindpaw of rats. Flinching responses were measured from 0-10 min (phase I, an initial acute state) and 11-60 min (phase II, a prolonged tonic state). To observe which opioid receptors are involved in the anti-nociceptive effect of i.t. N/OFQ in the rat-formalin tests, naltrindole (5-20 nmol), beta-funaltrexamine (1-10 nmol), and norbinaltorphimine (10 nmol), selective delta-, micro- and kappa-opioid receptor antagonists, respectively, were administered intrathecally 5 min after i.t. N/OFQ. RESULTS: I.t. N/OFQ attenuated the formalin-induced flinching responses in a dose-dependent manner in both phases I and II. I.t. administration of naltrindole and beta-funaltrexamine dose-dependently reversed the N/OFQ-induced attenuation of flinching responses in both phases; however, norbinaltorphimine did not. CONCLUSION: I.t. N/OFQ exerted an antinociceptive effect in both phases of the rat-formalin test through the nociceptin opioid peptide receptor. In addition, the results suggested that delta- and micro-opioid receptors, but not kappa-opioid receptors, are involved in the antinociceptive effects of N/OFQ in the spinal cord of rats.


Subject(s)
Analgesics/administration & dosage , Animals , Formaldehyde/toxicity , Injections, Spinal , Male , Naltrexone/administration & dosage , Narcotic Antagonists/administration & dosage , Opioid Peptides/administration & dosage , Pain Measurement , Rats , Rats, Sprague-Dawley , Receptors, Opioid/agonists
15.
Acta cir. bras ; 27(9): 600-605, Sept. 2012. ilus
Article in English | LILACS | ID: lil-646724

ABSTRACT

PURPOSE: To investigate the effect of the opioid blocker naltrexone in the inflammatory response in acute pancreatitis (AP). METHODS: Acute pancreatitis was induced in anesthetized male Wistar rats by retrograde injection of 2.5% sodium taurocholate diluted in 0.5ml saline into the main pancreatic duct. Animals were randomized to the following experimental groups: Control Group (n=9): animals received an intraperitoneal injection of saline solution (0.5ml), 15 minutes before the induction of AP. Naltrexone Group (n=9): animals received an intraperitoneal injection of naltrexone 0.5ml (15 mg/kg), 15 minutes before induction of AP. Peritoneal levels of TNF-α and serum levels of IL-6 and amylase were determined The volume of the ascitic fluid was also evaluated. Myeloperoxidase (MPO) activities were analyzed in homogenates of pulmonary tissue. RESULTS: There were no significant differences in the ascitic fluid volume, nor in TNF-a and IL-6 levels in the naltrexone group compared to controls. Treatment with naltrexone did not affect the lung MPO activity compared to control group. CONCLUSIONS: The opioid receptors don't play an important role in the pathogenesis of the inflammatory response in acute pancreatitis. If opioids affect leukocytes inflammatory signaling, there are no major implications in the pathogenesis of acute pancreatitis.


OBJETIVO: Investigar o efeito do bloqueador opióide naltrexone na resposta inflamatória da pancreatite aguda. METODOS: Pancreatite aguda foi induzida em ratos machos Wistar, através de injeção retrógada de solução de taurocolato de sódio a 2,5% nos ductos pancreáticos. Os animais foram alocados em dois grupos: Grupo controle (n=9) animais receberam 0,5 ml de solução salina intra-peritonial 15 minutos antes da indução da pancreatite aguda e Grupo naltrexone (n=9) animais receberam naltrexone (15mg/kg de peso), em 0,5 ml de volume final por via intraperitoneal, 15 minutos antes da indução da pancreatite aguda. Foram avaliados o volume de ascite, os níveis séricos de amilase e IL-6, assim como TNF-α peritoneal e a atividade da mieloperoxidase (MPO) no tecido pulmonar. RESULTADOS: Não foram encontradas diferenças significantes nos parâmetros analisados entre o grupo que recebeu solução salina e o que recebeu naltrexone . CONCLUSÕES: Os receptores opióides não desempenham papel importante na resposta inflamatória sistêmica associada à pancreatite aguda. Se os opioides alteram a sinalização inflamatória nos leucócitos está ação não se reflete na patogênese da pancreatite aguda.


Subject(s)
Animals , Male , Rats , Naltrexone/pharmacology , Narcotic Antagonists/pharmacology , Pancreatitis/etiology , Receptors, Opioid/physiology , Acute Disease , Amylases/blood , Disease Models, Animal , /blood , Pancreatitis/metabolism , Peroxidase/analysis , Random Allocation , Rats, Wistar , Receptors, Opioid/antagonists & inhibitors , Taurocholic Acid , Tumor Necrosis Factor-alpha/analysis
16.
Article in Korean | WPRIM | ID: wpr-45686

ABSTRACT

Opioid receptors have been pharmacologically classified as micro, delta, kappa and epsilon. We have recently reported that the antinociceptive effect of morphine (a micro-opioid receptor agonist), but not that of beta-endorphin (a novel micro/epsilon-opioid receptor agonist), is attenuated by whole body irradiation (WBI). It is unclear at present whether WBI has differential effects on the antinociceptive effects of micro-, delta-, kappa- and epsilon-opioid receptor agonists. In our current experiments, male ICR mice were exposed to WBI (5Gy) from a 60Co gamma-source and the antinociceptive effects of opioid receptor agonists were assessed two hours later using the hot water (52degrees C) tail-immersion test. Morphine and D-Ala2,N-Me-Phe4,Gly-olenkephalin(DAMGO), [D-Pen2-D-Pen5]enkephalin (DPDPE), trans-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide (U50,488H), and beta-endorphin were tested as agonists for micro, delta, kappa, and epsilon-opioid receptors, respectively. WBI significantly attenuated the antinociceptive effects of morphine and DAMGO, but increased those of beta-endorphin. The antinociceptive effects of DPDPE and U50,488H were not affected by WBI. In addition, to more preciously understand the differential effects of WBI on micro- and epsilon-opioid receptor agonists, we assessed pretreatment effects of beta-funaltrexamine (beta-FNA, a micro-opioid receptor antagonist) or beta-endorphin1-27 (beta-EP1-27, an epsilon-opioid receptor antagonist), and found that pretreatment with beta-FNA significantly attenuated the antinociceptive effects of morphine and beta-endorphin by WBI. beta-EP1-27 significantly reversed the attenuation of morphine by WBI and significantly attenuated the increased effects of beta-endorphin by WBI. The results demonstrate differential sensitivities of opioid receptors to WBI, especially for micro- and epsilon-opioid receptors.


Subject(s)
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer , Animals , beta-Endorphin , Enkephalin, Ala(2)-MePhe(4)-Gly(5)- , Enkephalin, D-Penicillamine (2,5)- , Humans , Male , Mice , Mice, Inbred ICR , Morphine , Naltrexone , Receptors, Opioid , Water , Whole-Body Irradiation
17.
Article in Korean | WPRIM | ID: wpr-123768

ABSTRACT

Opioids are the one of the most commonly used drugs to control cancer pain all over the world. But, we should not overlook the potential risk of opioid intoxication because they have well-known detrimental side effects. The opioid intoxication can be diagnosed thorough various clinical manifestations. The altered mental status, respiratory depression, and miosis is very representative clinical features although these symptoms don't always appear together. Unfortunately the opioid-toxidrome can be varied. A 42 years old man came to our emergency room after taking about 900 mg morphine sulfate per oral. He was nearly alert and his respiration was normal. Even though his symptoms didn't deteriorated clinically, serial arterial blood gas analysis showed increase in PaCO2. So we decided to use intravenous naloxone. Soon, he was fully awaked and his pupils size was increased. After a continuous infusion of intravenous naloxone for 2 hours, PaCO2 decreased to normal range and his pupil size also returned to normal after 12 hours. Though the levels of serum amylase and lipase increased slightly, his pancreas was normal according to the abdominal computed tomography. He had nausea, vomit, and whole body itching after naloxone continuous infusion, but conservatively treated. We stopped the continuos infusion after 1 day because his laboratory results and physical examinations showed normal. As this case shows, it is very important to prescribe naloxone initially. If you suspect opioid intoxication, we recommend the initial use of naloxone even though a patient has atypical clinical features. In addition, we suggest intranasal administration of naloxone as safe and effective alternative and it's necessary to consider nalmefene that has a longer duration for opioid intoxication.


Subject(s)
Administration, Intranasal , Amylases , Analgesics, Opioid , Blood Gas Analysis , Emergencies , Humans , Lipase , Miosis , Morphine , Naloxone , Naltrexone , Nausea , Pancreas , Physical Examination , Porphyrins , Pruritus , Pupil , Reference Values , Respiration , Respiratory Insufficiency
18.
Chinese Journal of Oncology ; (12): 425-429, 2012.
Article in Chinese | WPRIM | ID: wpr-307370

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of DADLE, a δ-opioid receptor agonist, on the proliferation of human liver cancer HepG2 cells and explore the mechanism involving PKC pathway.</p><p><b>METHODS</b>HepG2 cells were treated with DADLE at different doses (0.01, 0.1, 1.0 and 10 µmol/L). Cell viability was determined using methyl thiazolyl terazolium (MTT) assay. The expression of PKC mRNA and p-PKC protein were examined by RT-PCR and Western blot assay. After treated separately with DADLE plusing NAL or PMA, the cell cycle of HepG2 cells was analyzed by flow cytometer. MTT was used to detect their proliferation capacity and Western blot was used to examine the p-PKC expression. The growth inhibitory rate of HepG2 cells treated with DADLE and cis-diammine dichloridoplatinum (CDDP) was analyzed.</p><p><b>RESULTS</b>DADLE at different concentrations showed an inhibitory effect on the proliferation of HepG2 cells though inhibiting the expression of PKC mRNA and p-PKC protein. The results of flow cytometry showed that compared with the control group, the percentage of S + G(2)/M cells in DADLE-treated group was lowered by 3.94% (P < 0.01). Meanwhile, after treated with NAL and PMA, the percentage was elevated by 3.22% and 3.63%, respectively (P < 0.01). The MTT and Western blot assays showed that compared with the control group, the values of A570 and p-PKC protein levels in the HepG2 cells of DADLE-treated group were significantly decreased (P < 0.01). After treatment with NAL and PMA, the values of A570 and p-PKC protein levels were elevated significantly (P < 0.01). The growth inhibitory rate of DADLE + CDDP group was 79.9%, significantly lower than 25.2% and 43.2% of the DADLE and CDDP groups, respectively.</p><p><b>CONCLUSIONS</b>Activation of δ-opioid receptor by DADLE inhibits the apoptosis of human liver cancer HepG2 cells. The underlying mechanism may be correlated with PKC pathway. DADLE can enhance the chemosensitivity of HepG2 cells to CDDP.</p>


Subject(s)
Antineoplastic Agents , Pharmacology , Cell Cycle , Cell Proliferation , Cisplatin , Pharmacology , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm , Enkephalin, Leucine-2-Alanine , Pharmacology , Hep G2 Cells , Humans , Naltrexone , Pharmacology , Phosphorylation , Protein Kinase C , Genetics , Metabolism , RNA, Messenger , Metabolism , Receptors, Opioid, delta , Signal Transduction , Tetradecanoylphorbol Acetate , Pharmacology
19.
Rev. colomb. anestesiol ; 39(2): 251-257, mayo-jul. 2011.
Article in English, Spanish | LILACS | ID: lil-594595

ABSTRACT

Introducción. El prurito es una complicación frecuente de las patologías hepáticas, que puede llegar a ser de difícil manejo. El incremento en el tono opioide cerebral se ha postulado como mecanismo fisiopatológico causal del prurito. Es así como el antagonismo opioide causa mejoría y resolución sintomática en estos pacientes. Objetivo. Describir el manejo de prurito severo con antagonismo opioide en una paciente refractaria a manejo médico convencional, y hacer una revisión de la literatura. Metodología y resultados. Este es el caso de una paciente de 50 años de edad, con antecedente de hepatitis autoinmune, quien se presenta con historia de cinco años de prurito severo secundario a colestasis, manejada con antihistamínicos, esteroides, ácido ursodeoxicólico y colestiramina sin mejoría. Se decide manejo con antagonismo opioide; se inicia con naloxona infusión por 24 horas, con dosis ascendentes desde 0,002 mcg/ kg/min, hasta 0,2 mcg/kg/min, y posteriormente naltrexona, hasta dosis de 50 mg día. Se evalúo la respuesta terapéutica por medio de escala visual análoga (EVA). Desde el inicio de la infusión se obtiene disminución en la EVA hasta valores de 0/10 durante las primeras 24 horas, con mejoría clínica y sintomática.Conclusiones. En el enfoque de la paciente con prurito refractario debe considerarse el uso de antagonismo opioide como alternativa terapéutica.


Introduction. Pruritus is a frequent complication in liver disease and may be difficult to manage. Increased cerebral opiod tone has been proposed as the physiological mechanism that causes pruritus. Opiod antagonism, therefore, leads to an improvement and resolution of symptoms in these patients. Objective. Describe the management of severe pruritus using opiod antagonists in a patient who does not respond to conventional medical management, and conduct a review of the literature.Methodology and results. This is the case of a 50 year-old female patient with a history of autoimmune hepatitis with a five-year history of severe pruritus secondary to cholestasis whichdoes not improve after management with antihistamines, steroids, ursodeoxycholic acid and cholestyramine. It is decided to initiate management with opiod antagonists, starting with an infusion of naloxone for 24 hours with dose escalation from 0.002 μg/kg/min up to 0.2 μg/kg/min, followed by naltrexone up to a dose of 50 mg/day. The therapeutic response was assessed using the visual analog scale (VAS). Within 24 hours ofinitiating the infusion, there is a reduction in the VAS score down to 0/10, with clinical and symptomaticimprovement. Conclusions. The approach to patients with refractorypruritus should include the use of opioidantagonists as a therapeutic option.


Subject(s)
Humans , Male , Female , Young Adult , Middle Aged , Analgesics, Opioid , Naloxone , Naltrexone , Pruritus , Analgesics , Analgesics, Opioid , Pruritus
20.
Acta sci., Biol. sci ; 33(2): 219-225, Apr. - Jun. 2011.
Article in English | LILACS | ID: biblio-875385

ABSTRACT

The Sertoli cell has fundamental importance to the development and maintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal period through-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine and reproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1) during fetal and neonatal period in Wistar rats. According to the results, the manipulation of opioidergic system during pre-natal period reduced the total length of seminiferous tubule and Sertoli cell population in adult rats, but sperm production was normal because this cell has had a compensatory response for spermatozoids support capacity.


As células de Sertoli têm fundamental importância para o desenvolvimento e manutenção da espermatogênese, bem como possuem uma relação numérica diretamente proporcional com a produção espermática. O período proliferativo destas células em ratos ocorre entre 13 dias pré-natal e 21 dias pós-natal, resultando na definição da população de células de Sertoli nos animais adultos. As células de Leydig podem modular a proliferação das células de Sertoli durante o período fetal e neonatal por meio da -endorfina. A manipulação do sistema opioidérgico durante esta fase pode promover alterações em parâmetros relacionados com o desenvolvimento dos sistemas nervoso, endócrino e reprodutivo. Em virtude disto, o objetivo do presente trabalho foi comparar os efeitos do bloqueio de receptores opioides nas células de Sertoli, utilizando o naltrexone (50 mg kg-1), durante o período proliferativo destas células em ratos Wistar. De acordo com nossos resultados, a manipulação do sistema opioidérgico durante o período pré-natal reduziu o comprimento total de túbulos seminíferos e a população de células de Sertoli em ratos adultos, porém, a produção espermática foi normal pela resposta compensatória desta célula na capacidade de suporte para espermatozoides.


Subject(s)
Rats , Naltrexone , Spermatogenesis , Testis
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