• The Korean Journal of Pharmacology
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• v.16 no.1 s.26
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• pp.15-24
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• 1980

As it has been reported that opioids such as morphine and methionine-enkephalin induced antidiuresis and antinatriuresis along with decrease in renal hemodynamics when given intracerebroventricularly(ivt), the renal action of ivt naloxone, a pure antagonist of morphine, and its influence upon the morphine action were investigated in this study. Less than $0.3{\mu}M/kg$ naloxone ivt did not change renal funtion. $1{\mu}M/kg$ ivt tended to, increase urine flow rate and induce transient natriuresis. $3{\mu}M/kg$ ivt produced transient: natriuresis. $3{\mu}M/kg$ ivt produced marked diuresis and natriuresis without any changes of renal hemodynamics. $10{\mu}M/kg$ ivt produced significant increases of urine flow rate and excretion of sodium without any changes of renal hemodynamics. Morphine $0.03{\mu}M/kg$ ivt produced marked decrement in renal hemodynamics along with decreases of water and sodium excretion, as previously shown by Kang. These effects of ivt morphine were completely abolished by the pretreatment with $0.3{\mu}M/kg$ naloxone. These observations provide further evidence that opiate receptors and endorphins in the brain might play an important role in the center-mediated regulation of the renal function in the rabbit.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.45-50
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• 1982

Yeum et al. formulated a new hot-plate method using the threshold temperature, and there are some controversies on the effects of naloxone and diazepam on the antinociceptive action. In this paper, the comparison of three methods registering analgesic activity and the application of the new hot-plate method formulated by Yeum et al. on the study of the influences of naloxone and diazepam on the analgesic effect of morphine were tried in male mice. The results obtained were summarized as follows; 1) The least-square regression lines of the morphine analgesia plotted against log-dose showed the correlation coefficient of above 0.90, but the competitive antagonism produced by naloxone (0.1 mg/kg) against the analgesia was more prominently demonstated by the new hot-plate method than the other methods: original hot-plate method and electrical stimulation method. 2) In the experiment using the new hot-plate method, the log dose-response curve of morphine (y=7.30 x+49.80, r=0.998) was shifted to the right by the pretreatment of naloxone (0.1 mg/kg), but was slightly shifted to the left by the pretreatment of diazepam (2.5 mg/kg). This study suggests that for the analgesia experiment, the new hot-plate method is superior to the original hot-plate method or the electrical stimulation method, and that the potentiative effect of diazepam on the morphine anagesia is not significant.

• The Korean Journal of Pain
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• v.19 no.2
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• pp.187-191
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• 2006

Background: Patient-controlled epidural analgesia (PCEA), using a local anesthetic-opioid mixture, has been effectively applied after total knee replacement (TKR) surgery, which is associated with intense postoperative pain that requires postoperative analgesia for both rehabilitation and the pain itself. However, adverse opioid-related effects, such as nausea, vomiting and pruritus, are commonly encountered. It was our hypothesis that the adverse opioid-related effects could be reduced by the addition of naloxone, an opioid antagonist, to a mixture of fentanyl-ropivacaine PCEA. Methods: In 120 patients undergoing elective TKR surgery, epidural or combined spinal-epidural (CSE) anesthesia was performed and PCEA applied. In the control group (n = 65), 0.16% ropivacaine and $3{\mu}g/ml$ fentanyl ($2.4{\mu}g/ml$ for those older than 65 yrs) were administered. In the naloxone group (n = 55), naloxone ($2{\mu}g/ml$) was coadministered with the above regimen. The incidence and severity of postoperative nausea and vomiting, and the frequency of pruritus, the visual analog score (VAS) and the PCEA volume used were assessed 6 and 24 hrs after surgery. Results: The incidence of nausea and vomiting during the early postoperative period, and those of pruritus during the late postoperative period were significantly lower in the naloxone group. The VAS pain scores, the PCEA volume used and amount of rescue IV meperidine were similar in the two groups. Conclusions: A small dose of naloxone mixed with an opioid significantly reduces the incidence and severity of adverse opioid-related effects in PCEA, without reducing the analgesic effect.

• Journal of the korean academy of Pediatric Dentistry
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• v.25 no.2
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• pp.467-475
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• 1998

악안면 영역에 동통이 가하여지면 회피반사의 일종인 개구반사가 유발되며, 개구반사의 크기는 뇌간의 중추에 전달된 동통의 크기에 비례한다. 따라서 동통의 정도를 악이복근의 근전도를 이용하여 정량화 할 수 있고 동통의 지표로 이용할 수 있다. 본 실험은 악안면동통에 의하여 유발된 개구반사의 크기가 침점(족삼리) 전기자극으로 감소되는지와 이러한 전기침의 효과가 나타나는데 opioid 물질이 관여하는지에 대하여 연구하고자 하였다. 8주 이상, 150g이상의 Sprague-Dawley계 쥐 34 마리를 암수 구별없이 이용하여 실험하였다. 복강 내 Urethane용액(1.5g/kg)을 주입 전신마취하고 악이복근을 노출시켜 근전도 기록을 위한 한쌍의 선전극을 삽입하였다. 동통유발을 위하여 구강내 하악 이공주변에 0.1mm의 선전극을 한쌍 삽입하고 전기자극기에 연결하였다. 유해자극 조건은 duration $100{\mu}sec$, interval 5sec의 pulse로 정하고 자극의 크기는 개구반사를 일으키는 역치의 2배 크기로 하며 매 측정시마다 동일 자극을 10회식 가하여 평균하였다. 침점의 전기자극을 위하여 침점의 하나인 족삼리(Zusanli)에 표면전극(넓이 $0.4cm^2$ 정도)을 부착하고 자극부위가 약한 근수축을 일으키는 강도인 $100{\mu}sec$, 5V, 2Hz의 자극을 20분간 가하였다. 악이복근의 근전도는 교류증폭기 (Dam80, WPI, USA) 에서 1000배 증폭하여 유해자극이 가해진 순간 oscilloscope 에서 관찰하여 그 크기를 측정하였다. 침점의 전기자극으로 나타나는 진통효과가 opioid의 분비와 관련있는지 알아보기 위하여 opioid 의 길항제인 naloxone(0.2mg/kg)을 복강 내로 투여하였다. 실험군을 4군(group I - IV)으로 분류하였고 각 군에서 근전도를 측정한 단계는 다음과 같다. group I : control 침점에 전기자극 20 분간 가한후(EA), 20분후(EA20) group II : control 침점에 전기자극 20분간 가한후(EA), naloxone 투여 20분후(NX) group III : control naloxone 투여 5분후 침점에 전기자극 20분 가한후(NxEA20) group IV : control naloxone 투여 20분후(NX20) 구강내에 가해진 유해자극에 의하여 발생하는 악이복근 근전도는 족삼리 침점의 전기자극으로 그 크기가 감소하였고 이러한 침점자극의 효과는 naloxone의 투여로 인하여 억제되었다. 이와 같은 결과는 침점자극으로 진통작용이 나타나는데에 opioid 물질이 관여하고 있음을 시사한다.

• The Korean Journal of Zoology
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• v.34 no.3
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• pp.426-431
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• 1991

The present study examines the effect of naloxone, mu-opioid receptor antagonist, on prolactin (PRL) gene expression and secretion induced by estradiol (I) treahent in vivo. Adult rats were ovariectomized (OW) and implanted with Silastic capsules containing either vehicle (oil) or E. Three days later, NAL (2 mg/kg BW) or saline urere injected 30 min prior to sacrifice. To examine PRL secretion in vitro, the pituitaries were incubated in the superfusion system for 3 hrs. Superfusates were collected at 10 min intenrals on ice and subjected to PRL radioimmunoassay. Endogenous release of PRL in OU( + I rats was signifcantlv higher than that in OVX rats (mean $\pm$ SE; 24.5 $\pm$ 3.1 vs 14.5 $\pm$ 2.9 ns/10 min). A single injection of NAL clearly inhibited PRL release in Nitro from pituitaries derived from OW + I rats, but not from OW group. PRL myNA was determined by RNA-blot hybridisation assay with nicktranslated PRL CDNA. E stimulated PRL mRNA about 3 fold over that shown in OW group. Treahent of NAL suppressed the I-stimulated PRL myNA in OVX + I group, but not in OVX group. These data clearly showed that the NAL-induced inhibition of PRL secretion was well correlated with changes in PRL mRNA level and this inhibitory process appears to be mediated in I-dependent manner.

• The Journal of Korean Physical Therapy
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• v.6 no.1
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• pp.5-15
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• 1994

The purpose of this study was to examine the effect of electroanalgeia and $\beta-endorphin$ action by acupuncture-like (Lof/Hil) transcutaneous electrical nerve stimulation (TENS) applied to acupuncture points. Twelve healthy adult male aged between 19 ann 25 were randomly assigned to TENS group (n=6) and naloxone group (n=6). Subjects of both groups were strongly stimulated TENS with 4 pps and $200{\mu}s$ for 30 minutes on the LI 3 and LI 10 meridian points of dominant am. Naloxone group was injected naloxone hydrochloride before TENS application. The experimental pain threshold was measured by chronaxie meter CX-2 on the distal end of radius just before and after TENS application. The levels of plasma $\beta-endorphin$ and ACTH. serum cortisol and urinary 17-OHCS were analyzed by radioimmunoassay (RIA) kits before and after TENS application. In TENS group, there was a significant increase of experimental pain threshold (p<0.01), plasma $\beta-endorphin$ level (p<0.05), serum cortisol level (p<0,001) and urinary 17-OHCS levels (p<0.05) after TENS application. The plasma ACTH level was not significantly increased, but it showed an increasing tendency. In naloxone group, although there was a decreasing trend, ACTH and cortisol level did not show a significant change, but $\beta-endorphin$ and 17-OHCS level were significantly decreased (p<0.01). The result of this study stewed that acupuncture-like TENS induced analgesic effect, such that the levels of plasma $\beta-endorphin$, plasma ACTH, serum cortisol and urinary 17-OHCS were concomitantly increased with experimental pain threshold. It is suggested that the analgesic mechanism of the acupuncture-like TENS probably related to endogenous opioid component such as $\beta-endorphin$.

• The Korean Journal of Pain
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• v.32 no.2
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• pp.105-112
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• 2019

Background: Severe pain always develops after thoracotomy; intrapleural regional analgesia is used as a simple, safe technique to control it. This study was performed to evaluate whether a small dose of naloxone with local anesthetics prolongs sensory blockade. Methods: A prospective, randomized double-blinded controlled study was conducted on 60 patients of American Society of Anesthesiologists statuses I and II, aged 18 to 60 years, scheduled for unilateral thoracotomy surgery. After surgery, patients were randomly divided into two groups: through the intrapleural catheter, group B received 30 ml of 0.5% bupivacaine, while group N received 30 ml of 0.5% bupivacaine with 100 ng of naloxone. Postoperative pain was assessed using the visual analog pain scale (VAS). Time for the first request for rescue analgesia, total amount consumed, and incidence of postoperative complications were also recorded. Results: The VAS score significantly decreased in group N, at 6 h and 8 h after operation (P < 0.001 for both). At 12 h after injection, the VAS score increased significantly in group N (P < 0.001). The time for the first request of rescue analgesia was significantly longer in group N compared to group B (P < 0.001). The total amount of morphine consumed was significantly lower in group N than in the bupivacaine group (P < 0.001). Conclusions: Addition of a small dose of naloxone to bupivacaine in intrapleural regional analgesia significantly prolonged pain relief after thoracotomy and delayed the first request for rescue analgesia, without significant adverse effects.

• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.123-131
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• 1987

The possible inolvement of central opiate system in the control of cardiovascular function and in the antihypertensive action of clonidine has been examined in unanesthetized rats with shamoperated or 2-kidney, 1-clip (2K1C) renal hypertension. In both groups of rats, intraventricular clonidine $(3-30\;{\mu}g/kg)$ produced hypotension and bradycardia. Hypotensive action of clonidine was more potent in the hypertensive rats than in the normotensive sham-operated rats. Yohimbine $(30\;{\mu}g/kg,\;i.v.t.)$ inhibited the hypotension and bradycardia produced by clonidine. Naloxone ($50\;{\mu}g/kg$, i.v.t.) inhibited the action of clonidine in 2K1C hypertensive rats but not influenced in the sham-operated rats. Intraventricular morphine $(10-100\;{\mu}g/kg)$ also reduced rats. Intraventricular morphine $(10-100\;{\mu}g/kg)$ also reduced blood pressure and heart rate in both groups of rats. But these effects were not affected by yohimbine, but antagonized by naloxone ($50\;{\mu}g/kg$, i.v.t.). Chronic treatment of 2K1C rats with clonidine ($3{\times}20\;{\mu}g/kg$, p.o.,) for 14 days from 1 day after 2K1C operation) suppressed the development of hypertension and maintained the blood pressure in normal level and this errect of clonidine was abolished by naloxone (2 mg/kg, i. p.). In the 2K1C hypertensive rats, immunoreactive ${\beta}-endorphin$ content was significantly decreased, but maximum binding (Bmax) of $(^3H)-naloxone$ was significantly increased in brain of 2K1C hypertensive rats. However, Kd value was not changed. These results suggest that the opioidergic component might be involved in the antihypertensive action of clonidine only in hypertensive and that central opiate system might play important roles in pathophysiology of development and maintenance of hypertension.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.33-44
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• 1982

The binding in vitro of an opiate agonist, $(^3H)-morphine$, was studied using rat brain slices which were incubated in the modified Krebs-Henseleit bicarbonate buffer solution containing various concentrations of electrolytes with or without morphine, naloxone or morphine+naloxone at $4^{\circ}C$ for 24 hours. The binding of $(^3H)-morphine$ may be seperated into two component; one a saturable binding and the other nonsaturable. The saturable binding may be calculated from the differences in binding observed in the absence and presence of high concentration of morphine. The maximal saturable binding and $K_D$ value in the naive preparations were $0.32{\pm}0.02\;pmole/mg$ protein and $0.75{\pm}0.07\;nM$ respectively. The saturable binding of $(^3H)-morphine$ was significantly increased by low temperature-treatment, while $K_D$ value was not changed. Morphine in the incubation media significantly increased the saturable binding of $(^3H)-morphine$ and $K_D$ value. Naloxone also increased the maximal saturable binding of $(^3H)-morphine$ and $K_D$ value of the drug. Decrease of $K^+\;and\;Mg^{++}$, and addition of $Mn^{++}$ in the incubation media significantly increased the saturable binding of $(^3H)-morphine$, but decrease of $Na^+$and increase of $Ca^{++}$ in the incubation media did not influence the binding. The increment of the saturable binding of $(^3H)-morphine$ by nonlabeled morphine in the incubation media was notaffected by decrease of $Na^+,\;K^+\;or\;Mg^{++}$, or addition of $Mn^{++}$ into the incubation media, but was inhibited by increase of $Ca^{++}$ in the incubation media, while the increment of the saturable binding of $(^3H)-morphine$ was net observed by decrease of $Na^+,\;K^+\;or\;Mg^{++}$, or increase of $Ca^{++}$ in the incubation media. The above results indicate that change of opiate binding sites in quality, i.e. affinity, and quantity, i.e. number of binding sites, may occur by low temperature-treatment in the absence and presence of morphine or naloxone and that electrolytes play role of the changes of opiate binding sites.

• Journal of Veterinary Clinics
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• v.20 no.1
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• pp.22-25
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• 2003

The aims of this study were to investigate the efficacy of acupuncture on myoelectrical activity of inflamed or normal colon in the rat, and whether the effect of acupuncture on colonic motility was related to endogenous opioids. Twenty-two male Sprague-Dawley rats were divided into three groups. Experimental groups were normal group (n = 8), colitis group (n = 6) and naloxone group (n = 8). Stainless steel bipolar electrodes were implanted on the serosal layer of the proximal colon of rats. Colitis was induced 7 days after electrode implantation using trinitrobenzene sulphonic acid (TNBS) and ethanol. Electromyograms (EMG) were recorded by using polygraph 11 days after implantation of electrodes. In normal group, normal colonic motility was recorded for 60 min, and then traditional acupuncture at GV-1 was applied for 20 min and EMG was recorded for further 60 min in untreated rats. In colitis group, after recording of basal colonic motility for 60 min, 20 min of acupuncture treatment and further EMG recording was performed for 60 min in TNBS/ethanol treated rats. In naloxone group, following subcutaneous administration of naloxone (3 mg/kg), recording of EMG and acupuncture treatment were performed in TNBS/ethanol treated rats. In the normal group, acupuncture at GV-1 did not induce significant changes in colonic motility. TNBS/ethanol treatment had no significant effect on the frequency of colonic motility. And in colitis group, GV-1 acupuncture significantly decreased colonic motility (p < 0.01). In naloxone group, after injection of naloxone, acupuncture at GV-1 did not change colonic motility in TNBS/ethanol treated rats. On the inflamed colon, naloxone blocked the effect of acupuncture. The present results suggested that endogenous opioids released by acupuncture at GV-1 decrease the motility of inflamed colon in rats, but not normal colon.