The objectives of this study were to investigate the role of endogenous opioids in the mediation of stress-induced cardiomyopathy (SIC), and to evaluate which opioid receptors regulate heart resistance to immobilization stress. Wistar rats were subjected to 24 h immobilization stress. Stress-induced heart injury was assessed by 99mTc-pyrophosphate accumulation in the heart. The opioid receptor (OR) antagonists (naltrexone, NxMB - naltrexone methyl bromide, MR 2266, ICI 174.864) and agonists (DALDA, DAMGO, DSLET, U-50,488) were administered intraperitoneally prior to immobilization and 12 h after the start of stress. In addition, the selective micro OR agonists PL017 and DAMGO were administered intracerebroventricularly prior to stress. Finally pretreatment with guanethidine was used. Naltrexone did not alter the cardiac 99mTc-PP accumulation in stressed rats. NxMB aggravated stress-induced cardiomyopathy (P=0.005) (SIC). The selective micro OR agonist DALDA, which does not cross the blood-brain barrier, completely prevented (P=0.006) SIC. The micro OR agonist DAMGO exhibited weaker effect than DALDA. The selective delta ligand (DSLET) and kappa OR ligand (U-50,488) did not alter stress-induced 99mTc-pyrophosphate accumulation in the heart. Intracerebroventricular administration of the micro OR agonists aggravated SIC. Pretreatment with guanethidine abolished this effect (P=0.01). Guanethidine alone exhibited cardioprotective properties. A stimulation of central micro OR promotes an appearance of SIC. In contrast, stimulation of peripheral micro OR contributes to an increase in cardiac tolerance to stress.

• MeSH
• enkefalin, Ala(2)-MePhe(4)-Gly(5)- farmakologie   terapeutické užití   MeSH
• imobilizace škodlivé účinky   psychologie   MeSH
• kardiotonika farmakologie   terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• myokard metabolismus   MeSH
• naltrexon farmakologie   MeSH
• narkotika - antagonisté farmakologie   MeSH
• nemoci srdce chemicky indukované   metabolismus   prevence a kontrola   MeSH
• opioidní analgetika farmakologie   terapeutické užití   MeSH
• potkani Wistar MeSH
• psychický stres metabolismus   psychologie   MeSH
• receptory opiátové mu agonisté   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• enkefalin, Ala(2)-MePhe(4)-Gly(5)- MeSH
• kardiotonika MeSH
• naltrexon MeSH
• narkotika - antagonisté MeSH
• opioidní analgetika MeSH
• receptory opiátové mu MeSH

A short overview of new drugs approved for the treatment of obesity (lorcaserin, phentermine/topiramate combination) as well as those with a perspective for approval as antiobesity drugs (cetilistat, naltrexone/bupropion combination, liraglutide) is presented. All these drugs produce significant weight loss accompanied by reductions in cardiometabolic health risks. Although the adverse events were rather rare and tended to decrease with the duration of treatment with most of these medications, the drug-specific safety concerns should be seriously considered. In order to ensure an appropriate, efficient and safe implementation of novel antiobesity drugs into the comprehensive treatment of obesity, it will be necessary to establish a network of physicians and other health-care providers well educated in obesity management.

• Klíčová slova
• antiobesity drugs, cetilistat, liraglutide, lorcaserin, naltrexone/bupropion, phentermine/topiramate,
• MeSH
• benzazepiny terapeutické užití   MeSH
• benzoxaziny terapeutické užití   MeSH
• bupropion terapeutické užití   MeSH
• fentermin terapeutické užití   MeSH
• fixní kombinace léků MeSH
• fruktosa analogy a deriváty   terapeutické užití   MeSH
• glukagonu podobný peptid 1 analogy a deriváty   terapeutické užití   MeSH
• hmotnostní úbytek účinky léků   MeSH
• látky proti obezitě terapeutické užití   MeSH
• lidé MeSH
• liraglutid MeSH
• naltrexon terapeutické užití   MeSH
• obezita farmakoterapie   MeSH
• topiramat MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH
• úvodníky MeSH
• Názvy látek
• benzazepiny MeSH
• benzoxaziny MeSH
• bupropion MeSH
• cetilistat MeSH Prohlížeč
• fentermin MeSH
• fixní kombinace léků MeSH
• fruktosa MeSH
• glukagonu podobný peptid 1 MeSH
• látky proti obezitě MeSH
• liraglutid MeSH
• lorcaserin MeSH Prohlížeč
• naltrexon MeSH
• topiramat MeSH

Worldwide obesity prevalence has nearly doubled since 1980. Due to numerous co-morbidities, obesity represents a serious health and socioeconomic problem worldwide. Pharmacotherapy should be an integral part of comprehensive obesity management. Drug therapy can assist in weight loss and its maintenance in those individuals who do not achieve appropriate weight loss through lifestyle interventions alone. After the withdrawal of sibutramine from the market in 2010, orlistat, a lipase inhibitor, was the only remaining prescription drug approved for the long-term treatment of obesity. In 2012, phentermine/topiramate extended-release (PHEN/TPM ER) combination and lorcaserin were approved by the US FDA as novel medications for long-term weight management. Three major phase III trials conducted with each drug confirmed their efficacy in terms of weight loss/maintenance and improvement of cardiometabolic risks. No head-to-head studies between the two new anti-obesity drugs have been carried out. However, in the existing studies PHEN/TPM ER had a superior weight loss profile to lorcaserin but the incidence of adverse effects was lower with lorcaserin. Both drugs were well-tolerated, and adverse events were modest in intensity, dose dependent, rather rare, and tended to decrease with the duration of treatment. Major safety concerns regarding PHEN/TPM ER include elevations in resting pulse rate, teratogenicity, mild metabolic acidosis, and psychiatric and cognitive adverse events. Valvulopathy, cognitive impairment, psychiatric disorders, and hypoglycemia represent major safety concerns for lorcaserin. Although existing trials have not demonstrated any significant issues with PHEN/TPM ER-induced heart rate elevation and lorcaserin-induced valvulopathy, all safety concerns should be seriously taken into account in patients treated with either of these novel anti-obesity medications.

• MeSH
• benzazepiny škodlivé účinky   MeSH
• benzoxaziny škodlivé účinky   MeSH
• bupropion škodlivé účinky   MeSH
• farmaceutická chemie MeSH
• fentermin aplikace a dávkování   škodlivé účinky   MeSH
• fruktosa aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• glukagonu podobný peptid 1 škodlivé účinky   analogy a deriváty   MeSH
• látky proti obezitě aplikace a dávkování   škodlivé účinky   MeSH
• lidé MeSH
• liraglutid MeSH
• naltrexon škodlivé účinky   MeSH
• nežádoucí účinky léčiv MeSH
• obezita farmakoterapie   MeSH
• topiramat MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• benzazepiny MeSH
• benzoxaziny MeSH
• bupropion MeSH
• cetilistat MeSH Prohlížeč
• fentermin MeSH
• fruktosa MeSH
• glukagonu podobný peptid 1 MeSH
• látky proti obezitě MeSH
• liraglutid MeSH
• lorcaserin MeSH Prohlížeč
• naltrexon MeSH
• topiramat MeSH

According to a recent literature review on the opioid mechanism in eating disorders, we found that there is increasing reason to re-examine the treatment potential of naltrexone. The endogenous opioid system belongs to the important modulators of food intake. The eating disorders share many traits with substance dependence models. We present two case histories of time-limited naltrexone therapy to show that, in clinical practice, individualized indication may contribute to short-term improvement and to prediction of a different long-term treatment outcome.

• MeSH
• afekt účinky léků   MeSH
• alkoholismus komplikace   farmakoterapie   MeSH
• dospělí MeSH
• lidé MeSH
• naltrexon terapeutické užití   MeSH
• narkotika - antagonisté terapeutické užití   MeSH
• poruchy příjmu potravy komplikace   farmakoterapie   MeSH
• sebezhodnocení (psychologie) MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• naltrexon MeSH
• narkotika - antagonisté MeSH

Heroin treatment or abusive drug addiction influences many physiological functions, including the reactions of the immune system. Although suppression of various manifestations of the immune system after heroin (or morphine) administration has been reported, we show here that production of proinflammatory cytokines and nitric oxide (NO) was enhanced and allotransplantation reactions were accelerated significantly in heroin-treated recipients. Mice were treated by a subcutaneous administration of heroin (diacetylmorphine) given in one or repeated daily doses. The ability of spleen cells from treated mice to respond in vitro to alloantigens and to produce IL-2, IL-4, IL-10 and IFN-gamma, and the production of IL-1beta, IL-12 and NO by peritoneal macrophages, were tested. Within 2 h after heroin administration, proliferative responses to alloantigens and the production of IL-1beta, IFN-gamma, IL-12 and NO were enhanced significantly. In contrast, the production of anti-inflammatory cytokines IL-4 and IL-10 was at the same time rather decreased. As a consequence, skin allografts in heroin-treated mice were rejected more promptly than in untreated or vehicle-treated recipients. Similarly, the growth of allogeneic tumours induced by high doses of tumour cells was suppressed significantly in heroin-treated mice. The enhancing effects of heroin on the production of proinflammatory cytokines were antagonized by naltrexone, a specific inhibitor of classic opioid receptors. These results show that heroin treatment augments production of proinflammatory cytokines and accelerates allotransplantation reactions. The observations thus illustrate the complexity of the effects of heroin on the immune system and should be taken into account during medical treatment of opiate addicts and in the use of morphine to decrease pain in various clinical situations.

• MeSH
• cytokiny krev   MeSH
• experimentální nádory farmakoterapie   imunologie   MeSH
• fibrosarkom farmakoterapie   imunologie   MeSH
• heroin farmakologie   MeSH
• homologní transplantace MeSH
• interferon gama biosyntéza   MeSH
• interleukin-1 biosyntéza   MeSH
• interleukin-10 biosyntéza   MeSH
• interleukin-12 biosyntéza   MeSH
• interleukin-2 biosyntéza   MeSH
• interleukin-4 biosyntéza   MeSH
• kultivované buňky MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• naltrexon farmakologie   MeSH
• narkotika - antagonisté farmakologie   MeSH
• narkotika farmakologie   MeSH
• oxid dusnatý metabolismus   MeSH
• peritoneální makrofágy metabolismus   MeSH
• slezina imunologie   MeSH
• transplantace kůže imunologie   MeSH
• transplantační imunologie účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• heroin MeSH
• interferon gama MeSH
• interleukin-1 MeSH
• interleukin-10 MeSH
• interleukin-12 MeSH
• interleukin-2 MeSH
• interleukin-4 MeSH
• naltrexon MeSH
• narkotika - antagonisté MeSH
• narkotika MeSH
• oxid dusnatý MeSH

In order to assess thyroid function in former opioid addicts undergoing adjunctive naltrexone (NA) p.o. treatment, we studied 24 subjects (BMI +/- SD: 23.3 +/- 3.2 kg/m2) on 50 mg NA p.o. daily for 15 days to 14.5 months continuously. Measurements included thyrotropin (TSH), total thyroxin (TT4), total triiodothyronine (TT3), while the TT3/TT4100 ratio was calculated as a marker of peripheral conversion of T4 to T3. Reverse T3 (rT3) and serum interleukin-6 (IL-6) levels were also measured. Statistical analysis of thyroid parameters among them, of thyroid parameters versus duration of NA use as well as of thyroid parameters versus BMI was done with linear regression. All the subjects received NA well. The thyroid hormone work-up showed that all the subjects on NA were overall euthyroid. Mean +/- SD levels for TSH were 1.59 +/- 0.29 mU/L, TT4: 171.17 +/- 14.07 nmol/L, TT3: 2.01 +/- 0.27 nmol/L, TT3/TT4100: 1.18 +/- 0.19, rT3: 0.26 +/- 0.07 nmol/L and IL-6: 20.3 +/- 36.6 pg/mL. The duration of NA use was positively correlated with TT3 (r = +0.72, p < 0.001) and TT3/TT4 x 100 (r = +0.77, p < 0.001) and negatively, but not statistically significant, with TT4 (r = -0.38, p = 0.065) and with TSH (r = -0.39, p = 0.062). No significant correlations were found between TT3 and BMI, duration of NA use and rT3 and IL-6. Although few subjects were studied, there are indications that the duration of naltrexone may be positively correlated with TT3 and the ratio of T4 to T3 conversion.

• MeSH
• dospělí MeSH
• interleukin-6 krev   MeSH
• lidé MeSH
• naltrexon terapeutické užití   MeSH
• narkotika - antagonisté terapeutické užití   MeSH
• štítná žláza účinky léků   patofyziologie   MeSH
• thyreotropin krev   MeSH
• thyroxin krev   MeSH
• trijodthyronin krev   MeSH
• závislost na heroinu patofyziologie   rehabilitace   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• interleukin-6 MeSH
• naltrexon MeSH
• narkotika - antagonisté MeSH
• thyreotropin MeSH
• thyroxin MeSH
• trijodthyronin MeSH

• MeSH
• amenorea farmakoterapie   MeSH
• anovulace farmakoterapie   MeSH
• lidé MeSH
• naltrexon terapeutické užití   MeSH
• premenstruační syndrom farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• naltrexon MeSH

The administration of 550 mg naltrexon in the course of 13 days did not four patients with narcolepsy-cataplexy to improvement of symptoms of the disease and did not improve their appetite or increase their body weight. No side-effects of naltrexon were observed.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• naltrexon terapeutické užití   MeSH
• narkolepsie farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• naltrexon MeSH

• MeSH
• kóma chemicky indukované   metabolismus   MeSH
• králíci MeSH
• morfin farmakologie   MeSH
• naloxon farmakologie   MeSH
• naltrexon farmakologie   MeSH
• narkotika - antagonisté MeSH
• receptory opiátové metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• morfin MeSH
• naloxon MeSH
• naltrexon MeSH
• narkotika - antagonisté MeSH
• receptory opiátové MeSH

The effects of the acute and chronic administration of a pure opioid antagonist--naltrexone--was studied in chick embryos from the 4th to the 19th day of incubation. In acute administration, naltrexone (40 mg/kg egg weight) induced paroxysmal activation of spontaneous motility in both normal and spinal embryos from the 13th-15th day of incubation. Activation attained 3- to 4-fold the resting activity of chick embryos of the same ages. The chronic administration of naltrexone (7.46 +/- 1.18 mg/kg e.w. per 24 h) from the 4th to the 16th day of incubation was not manifested either in the embryos' somatic development or in the weight of the brain hemispheres, but it depressed the development of spontaneous motility to 26.1-75.8% of the activity of the control embryos. This developmental effect was not demonstrably correlated either to the length of time for which naltrexone was administered, or to when, in the course of incubation, it was administered to the chick embryos. The results are evaluated as evidence of the participation of opioid elements in the development and effectuation of central motor input functions in the early stages of ontogenetic development.

• MeSH
• časové faktory MeSH
• kuřecí embryo účinky léků   fyziologie   MeSH
• naltrexon aplikace a dávkování   farmakologie   MeSH
• pohyb účinky léků   MeSH
• receptory opiátové fyziologie   MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo účinky léků   fyziologie   MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• naltrexon MeSH
• receptory opiátové MeSH