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1.
羟甲芬太尼(I)是一个新的高强度高选择性阿片μ受体激动剂。本文用cis-A-N-[1-(2-羟基-2-苯乙基)-3-甲基-4-哌啶基]-苯胺(II)或cis-N-[1-(苯甲酰甲基)-3-甲基-4-哌啶基]-苯胺(III)作为前体合成了[11C]-羟甲芬太尼,以便用正电子发射断层扫描(PET)来观察μ受体。通过水解cis-A-羟甲芬太尼(I)和cis-N-[1-(苯甲酰甲基)-3-甲基-4-哌啶]-N-苯基丙酰胺(cis-IV)的4-N-丙酰基分别获得II和III。溴乙烷的格氏试剂与回旋加速器产生的[11C]-二氧化碳反应后继而直接加入邻苯二甲酸二酰氯和2,6-二叔丁基吡啶生成同位素标记中间体[11C]-丙酰氯。[11C]-丙酰氯与OH-前体(II)反应后再经HPLC分离纯化直接得[11C]-羟甲芬太尼;[11C]-丙酰氯与酮-前体(III)反应后,再用硼氢化钠甲醇溶液处理,然后进行HPLC分离纯化得[11C]-羟甲芬太尼。两种方法均可获得ll.1~14.8GBq/μmol的特异性放射化学纯[11C]-羟甲芬太尼。总共耗时为40~50min(EOB)。 相似文献
2.
Laurie Wermuth PhD Stephen Brummett MSW James L. Sorensen PhD 《Journal of substance abuse treatment》1987,4(3-4):189-196
Clinical issues are described in opiate addicts attempting to taper off methadone maintenance, and techniques are suggested to help this patient population. The observations were generated in an experimental “Tapering Network” project, in which opiate addicts on methadone maintenance had the opportunity to receive individual and group counseling, relapse prevention training, self-help groups, and other services. Vignettes illustrate clinical problems with intimacy and social isolation, identity as a former addict, and a “post methadone syndrome” characterized by vulnerability, dramatic swings in mood, and disordered thinking for a period of up to six months after detoxification. To counteract these barriers to recovery, a program model is suggested that uses curricula available in the emerging literature on treatment of substance abuse. These techniques can provide bridges to recovery. 相似文献
3.
4.
The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. We have recently shown that ‘illness’-inducing agents, such as intraperitoneally administered lipopolysaccharide (LPS; bacterial endotoxin), can produce prolonged hyperalgesia. This hyperalgesic state is mediated at the level of the spinal cord via activation of the NMDA-nitric oxide cascade. However, prolonged neuronal depolarization is required before such a cascade can occur. The present series of experiments were aimed at identifying spinal neurotransmitters which might be responsible for creating such a depolarized state. These studies show that LPS hyperalgesia is mediated at the level of the spinal cord by substance P, cholecystokinin and excitatory amino acids acting at non-NMDA sites. No apparent role for serotonin or kappa opiate receptors was found. 相似文献
5.
Despite the existence of a well-defined abstinence syndrome in offspring of opiate-dependent mothers, the mechanisms involved in neonatal abstinence remain unclear. The goal of the present study was to determine the contribution of noradrenergic neurons in the opiate abstinence syndrome in neonatal rats (10 days old). First, the ability of the α2-adrenergic agonist, clonidine to attenuate the symptoms of neonatal opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring postmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opiate abstinence was characterized by an increased incidence of wall climbing, tremors and mouthing. Acute treatment with morphine and naloxone in chronic saline-treated pups also produced the tremor, albeit less severe than in pups treated chronically with morphine. Clonidine (0.2 mg/kg) attenuated the expression of tremor and mouthing in neonates, but increased wall climbing. Clonidine elicited wall climbing in opiate-naive neonates. Treatment with morphine followed by naltrexone increased MHPG levels in all of the brain areas examined, irrespective of the chronic treatment, but naltrexone treatment elicited a larger increase in MHPG levels in pups treated chronically with morphine. Acute morphine treatment increased MHPG levels only in the hypothalamus. The results of the present study provide behavioral and neurochemical data supporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence. 相似文献
6.
We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study
with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice
between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate
drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37 ± 0.02 mg/kg per day, subordinate rats: 0.57 ± 0.05 mg/kg
per day) and environmental variables (group housing: 0.21 ± 0.02 mg/kg per day, single housing: 0.41 ± 0.03 mg/kg per day).
Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9 ± 0.2 mg/kg per day in week 47), although the experimental conditions
remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the
rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external
conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6 ± 0.6 mg/kg per day; age-matched controls:
0.37 ± 0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1 ± 0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during
withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42 ± 0.04 mg/kg per day).
Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol
and opiates.
Received: 3 April 1998/Final version: 26 August 1998 相似文献
7.
J. M. Maloteaux J. N. Octave E. C. Laterre P. M. Laduron 《Naunyn-Schmiedeberg's archives of pharmacology》1989,339(1-2):192-199
Summary There was stereospecific binding of 3H-lofentanil (K
D value = 1.53 nM) to membranes of neuroblastoma-glioma NG 108-15 cells which are known to bear high affinity binding sites for enkephalin derivatives (-opiate receptor subtype). There was no high affinity specific binding of the -opiate specific ligand 3H-sufentanil. The specific binding of 3H-lofentanil to -opiate receptor subtype was down-regulated (decrease in B
max value without change in the K
D value) after prolonged incubation of the cells in the presence of leu- and met- enkephalin (0.1 M). There was no down-regulation of the opiate receptors (3H-lofentanil and 3H-d-ala-d-leu-enkephalin specific binding) after incubation of NG 108-15 cells with drugs from the fentanyl series (alfentanil or sufentanil).In cultured neurones from rat forebrain (15 day old embryos), the 3H-lofentanil binding was specific with high affinity (K
D: 0.048 nM) and a slow dissociation rate similar to that in adult rat cortex. Drugs of the fentanyl series (4-anilino-piperidines) were potent displacers whereas agonists of the - (enkephalin derivatives), (phencyclidine, haloperidol, 3-hydroxyphenyl-propylpiperidine) or K- (U 50488) opiate sites had a low affinity (K
i > 0.5 M) for 3H-lofentanil specific binding sites. Since there was also specific binding of 3H-sufentanil, the opiate receptors in cultured neurones seem to be mainly of the -subtype and this is consistent with the ontogeny of opiate receptors subtypes. These receptors were down-regulated after incubation in the presence of etorphine, sufentanil and alfentanil but not enkephalin derivatives.These results strongly suggest specific binding of 3H-sufentanil and 3H-lofentanil mainly to the so-called -opiate receptors in cultured neurones and a specific binding of 3H-lofentanil to lower affinity -opiate receptors in neuroblastoma-glioma cells. The down-regulation of the -opiate binding sites in cultured neurones and that of the -site in neuroblastoma × glioma hybrid cells were dose-and temperature-dependent, induced by the corresponding high affinity agonists and prevented by naloxone. Morphine did not induce down-regulation of or receptor sites, possibly because of a partial antagonist effect on both receptor subtypes.
Send offprint requests to J. M. Maloteaux at the above address 相似文献
8.
M B Essatara J E Morley A S Levine M K Elson R B Shafer C J McClain 《Physiology & behavior》1984,32(3):475-478
Anorexia is a major symptom of zinc deficiency, but the mechanism(s) for this anorexia are poorly defined. Recent studies have suggested an integral role for endogenous opiate peptides in appetite regulation. Dynorphin, a leucine-enkephalin containing opiate peptide, is a potent inducer of spontaneous feeding. In this study we showed that zinc deficient animals were relatively resistant to dynorphin-induced feeding. Measurement of dynorphin levels using a highly sensitive radioimmunoassay showed that zinc deficient animals had lower levels of dynorphin in the hypothalamus than did ad lib fed animals, with weight restricted animals having intermediate values. [3H]-naloxone binding was significantly increased to isolated brain membranes from zinc deficient animals using 1 nM unlabeled naloxone when compared to ad lib fed controls with the weight restricted animals again having intermediate values. These data suggest that abnormalities in endogenous opiate regulation of appetite may well play a role in the anorexia of zinc deficiency. The effects of zinc deficiency on endogenous opiate action appear to include alterations in receptor affinity, a post-receptor defect and alterations in the synthesis and/or release of dynorphin. 相似文献
9.
The analgesic ED50 values of some classical morphine congeners (morphine, methadone, fentanyl, azidomorphine) in the rat and mouse tail-flick tests were found to be similar. However, several synthetic derivatives of the natural enkephalins were more potent in mice than in rats. (These analogs contain d-amino acid in position 2 and d- or l-sulfonic (or phosphonic) acid residue in position 5). -Endorpin, d-Met2, Pro5-enkephalinamide and two partial agonists showed intermediate interspecies relative potencies. According to the data obtained, similar opiate receptors might mediate the analgesic action of classical opiates in rats and in mice. However, the opiate receptors responsible for the antinociceptive effects of the above mentioned enkephalin analogues must be dissimilar in the two species examined. The results are discussed in terms of the role of - and -receptors in mediation of the analgesic effect induced by different types of opioids. 相似文献
10.
应用放射受体分析和体外受体放射自显影技术,研究了甲醛固定对阿片受体结合能力的影响。结果表明,1%多聚甲醛溶液中孵育30分钟或12小时,对大鼠脑膜阿片受体结合能力均无显著影响; 2%或4%多聚甲醛溶液中孵育30分钟,对阿片受体结合能力也无显著影响。经甲醛固定的脑切片上的阿片受体,与[~3H]-埃托啡结合的饱和曲线与新鲜脑切片的相似。用1%多聚甲醛固定的组织切片进行体外受体放射自显影,较好地显示了阿片受体的分布。这些结果提示,甲醛固定的组织可用于进行体外受体放射自显影研究。 相似文献