Pupillary effects of leucine and methionine enkephalin in rats after intraperitoneal administration

Changes in pupil size after peripheral administration of met-enkephalin, leu-enkephalin, or morphine were studied in the rat. With a simple pupillographic technique, the pupil diameter of male, S.D. rats (250–300 g) was measured by a series of photographs taken every 60 sec for at least 45 min after the last drug injection. Morphine (8 mg/kg, SC) caused mydriasis characterized by rapid and marked fluctuations of pupil size. Mydriasis also occurred after leu-enkephalin (5 and 10 mg/kg, IP) and met-enkephalin (20 mg/kg, IP). Both peptides induced morphine-like fluctuations. When given 15 min after morphine, leu-enkephalin (5 and 10 mg/kg) increased the mydriatic effect of morphine from 172 percent of control to 224 and 272 percent, respectively. Met-enkephalin (20 mg/kg, but not 10 mg/kg) also enhanced the mydriatic response of morphine, to 244 percent of control. These interactions appear to represent simple addition rather than potentiation. The effects of both peptides were reversed by naloxone (1 mg/kg, SC), suggesting an opiate receptor interaction for the pupillary effects of the enkephalins. The rat pupil thus provides one of the few in vivo models permitting quantification of enkephalin action after parenteral administration.     

Effects of intracranial self-stimulation on brain opioid peptides

The neurochemical system(s) underlying brain stimulation reward (ICSS) has been investigated for many years. The catecholamine hypothesis is currently most accepted with predominant emphasis on the role of dopamine. The present report examines the role of three opioid peptides--Methionine and Leucine Enkephalin (ME and LE) and beta-Endorphin (beta-E) in this behavior. Peptide levels from pituitary, hypothalamus and whole brain were determined by independent RIAs and analyzed according to treatment: low, moderate and high ICSS responders, sham controls, animals receiving nonspecific stimulation, and naloxone--with and without ICSS. Not only did naloxone reduce ICSS from high responders by 74%, it also was able to reduce peptide levels--most notably for ME and beta E in most regions. Additionally, the effects of ICSS on endorphin levels was found to be related to the rate category of responding. Since endorphins are known to interact with dopamine systems, it is therefore considered likely that the endogenous opioid peptides play an important role in ICSS either directly or indirectly via their influence on catecholamine systems.     

Reversal of morphine, methadone and heroin induced effects in mice by naloxone methiodide

Opioid overdose, which is commonly associated with opioid induced respiratory depression, is a problem with both therapeutic and illicit opioid use. While the central mechanisms involved in the effects of opioids are well described, it has also been suggested that a peripheral component may contribute to the effects observed. This study aimed to further characterise the effects of the peripherally acting naloxone methiodide on the respiratory, analgesic and withdrawal effects produced by various opioid agonists. A comparison of the respiratory and analgesic effects of morphine, methadone and heroin in male Swiss-Albino mice was conducted and respiratory depressive ED(80) doses of each opioid determined. These doses (morphine 9 mg/kg i.p., methadone 7 mg/kg i.p., and heroin 17 mg/kg i.p.) were then used to show that both naloxone (3 mg/kg i.p.) and naloxone methiodide (30-100 mg/kg i.p.) could reverse the respiratory and analgesic effects of these opioid agonists, but only naloxone precipitated withdrawal. Further investigation in female C57BL/6J mice using barometric plethysmography found that both opioid antagonists could reverse methadone induced decreases in respiratory rate and increases in tidal volume. Its effects do not appear to be strain or sex dependent. It was concluded that naloxone methiodide can reverse the respiratory and analgesic actions of a variety of opioid agonists, without inducing opioid withdrawal.     

小剂量纳洛酮硬膜外应用对胃癌术后芬太尼静脉自控镇痛效果及胃肠功能的影响

目的:探讨小剂量纳洛酮硬膜外应用对胃癌术后芬太尼静脉自控镇痛效果及胃肠功能的影响。方法:选取我院2010年7月-2015年7月收治的110例胃癌患者为研究对象,将所有患者随机分为试验组和对照组各55例,两组患者均行根治性肿瘤切除术,术后采用芬太尼静脉自控镇痛,试验组于术后硬膜外注入小剂量纳洛酮,对照组注入等量的生理盐水,对两组术后不同时间点(4 h、8 h、12 h、24 h)疼痛程度进行评分,对比两组肠鸣音恢复时间、肛门排气时间、肛门排便时间、胃动力恢复时间,镇痛泵药物消耗量及并发症发生率。结果:术后4 h,试验组疼痛评分明显低于对照组(P0.05),术后8 h、12 h两组患者的疼痛评分均有显著上升(P0.05),且试验组患者的疼痛评分均远低于对照组(均P0.05),术后24 h,试验组与术后12 h比较差异无统计学意义(P0.05),对照组术后24 h疼痛评分与术后12 h分相比有显著差异(P0.01);试验组患者肠鸣音恢复时间、肛门排气时间、肛门排便时间、胃动力恢复时间、镇痛泵药物消耗量、芬太尼用量均远远低于对照组(P0.05);试验组并发症总发生率(7.27%)远远低于对照组(23.64%),差异具有统计学意义(P0.05)。结论:采用小剂量纳洛酮硬膜外应用方法辅助术后镇痛可以有效的减轻患者的疼痛,降低并发症的发生率,促进胃肠功能恢复,疗效显著,值得在临床上推广使用。     

Attenuation of morphine analgesia by α-MSH,MIF-I,melatonin and naloxone in the rat

In two experiments the effects of the pituitary peptide α-MSH, the hypothalamic tripeptide MIF-I (P-L-G-NH₂) and the pineal hormone melatonin were investigated on the attenuation of morphine analgesia measured by a tail flick test. In Experiment 1, α-MSH had minimal effect on morphine analgesia, whereas, MIF-I and melatonin clearly delayed the onset of morphine analgesia, and melatonin also shortened the duration of analgesia. Experiment 2 was designed to investigate the possible synergistic effect of MIF-I and melatonin. The combined treatment of MIF-I and melatonin significantly delayed the onset of morphine analgesia, and melatonin alone shortened the duration of analgesia. The relationshps among the pituitary, hypothalamus and the pineal for the modulation of pain and response to morphine were discussed.     

Insulin and glucagon immunoreactivity during high-intensity exercise under opiate blockade

Eight fit men [maximum oxygen consumption (O_2max) 64.6 (1.9) ml · kg⁻¹ · min⁻¹, aged 28.3 (1.7) years (SE in parentheses) were studied during two treadmill exercise trials to determine the effect of endogenous opioids on insulin and glucagon immunoreactivity during intense exercise (80% O_2max). A double-blind experimental design was used with subjects undertaking the two exercise trials in counterbalanced order. Exercise trials were 20 min in duration and were conducted 7 days apart. One exercise trial was undertaken following administration of naloxone (N; 1.2 mg; 3 ml) and the other after receiving a placebo (P; 0.9% NaCl saline; 3 ml). Prior to each experimental trial a flexible catheter was placed into an antecubital vein and baseline blood samples were collected. Immediately after, each subject received either a N or P bolus injection. Blood samples were also collected after 20 min of continuous exercise (running). Glucagon was higher (P < 0.05), while insulin was lower (P < 0.05), during exercise compared with pre-exercise values in both trials. However, glucagon was higher (P < 0.05) in the P than in the N exercise trial [141.4 (8.3) ng · l⁻¹ vs 127.2 (7.6) ng · l⁻¹]. There were no differences in insulin during exercise between the P and N trials [50.2 (4.3) pmol · l⁻¹ vs 43.8 (5) pmol · l⁻¹]. These data suggest that endogenous opioids may augment the glucagon response during intense exercise. Accepted: 15 June 1996     

下丘脑前区的脑啡肽参与急性心肌缺血减弱颈动脉窦升压反射的效应

家兔急性心肌缺血时,下丘脑等脑区亮啡肽(L-Enk)含量显著升高,延脑未见明显变化,向下丘脑前区直接注射微量L-Enk,同阻断冠脉效应相同,也可减弱窦升压反射。该区注射纳络酮(Nx)可逆转心肌缺血减弱窦升压反射的效应,而对正常兔的窦升压反射没有明显影响。提示:急性心肌缺血时,下丘脑前区的脑啡肽可被激活,并参与窦升压反射的调节。但在正常情况下,这些脑啡肽可能处在非活动状态,在窦升压反射的调节中可能不起重要作用。     

Involvement of the hypothalamus in opiate-stimulated prolactin secretion

Administration of opiate agonists to rats is known to elevate plasma prolactin, an effect which is antagonised by the opiate antagonist naloxone. However, this appears not to be a result of a direct action at the pituitary gland. We report here that opiate agonists stimulate prolactin secretion from isolated adenohypophysial cells when they are coincubated with hypothalamic fragments. Both morphine and Met-enkephalin stimulated prolactin secretion by 1.84 fold and 1.50 fold respectively, and this was antagonised by naloxone. These findings support the hypothesis that one site of action of opioid compounds on pituitary hormone secretion is at the level of hypothalamus.     

纳洛酮对心搏骤停患者心肺复苏后氧化应激反应及缺血缺氧性脑病的影响

目的:探讨纳洛酮对心搏骤停患者心肺复苏(CPR)后氧化应激反应及缺血缺氧性脑病的影响。方法:将我院收治的78例骤停时间≤10 min的心搏骤停患者随机分为治疗组和对照组,每组各39例。两组均按照美国心脏学会心肺复苏指南进行标准的心肺复苏,治疗组在此基础上静脉注射纳洛酮2 mg,复苏后用纳洛酮0.4 mg/(kg·d)微量注射泵24h持续泵入。比较两组的CPR成功率、血浆丙二醛(MDA)含量和谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)活性,监测其不同时点脑氧摄取量(CEO2)的变化。结果:与对照组比较,治疗组自主循环恢复成功率、复苏后24 h存活率均显著升高(P<0.05)。自主循环恢复后,治疗组SOD、GSH-PX活性较对照组明显增加(P<0.05);复苏后24 h,两组MDA含量均显著升高,SOD、GSH-PX活性明显减弱,而治疗组各氧化应激指标明显优于对照组(P<0.05)。两组患者在复苏早期CEO2迅速升高,但在复苏后24 h开始下降,48~72 h处于相对稳定的水平,治疗组各时间点CEO2均明显高于对照组(P<0.05)。结论:纳洛酮可减轻心搏骤停患者CPR后体内氧化应激损伤和缺血缺氧性脑病,改善患者的预后。