• Archives of Pharmacal Research
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• v.28 no.6
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• pp.699-708
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• 2005

The present study was designed to investigate the effect of naloxone, a well known opioid antagonist, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal glands, and to establish its mechanism of action. Naloxone ($10^{-6}\~10^{-5}$ M), perfused into an adrenal vein for 60 min, produced dose- and time-dependent inhibition of CA secretory responses evoked by ACh ($5.32\times10^{-3}$ M), high K+ ($5.6\times10^{-2}$ M), DMPP ($10^{-4}$ M) and McN-A-343 ($10^{-4}$ M). Naloxone itself also failed to affect the basal CA output. In adrenal glands loaded with naloxone ($3\times10^{-6}$ M), the CA secretory responses evoked by Bay-K-8644, an activator of L-type $Ca^{2+}$ channels, and cyclopiazonic acid, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase, were also inhibited. In the presence of met-enkephalin ($5\times10^{-6}$ M), a well known opioid agonist, the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly inhibited. Taken together, these results suggest that naloxone greatly inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as that by membrane depolarization. It seems that these inhibitory effects of naloxone does not involve opioid receptors, but might be mediated by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of $Ca^{2+}$ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself.

• The Korean Journal of Pain
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• v.20 no.2
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• pp.123-129
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• 2007

Background: Postoperative pruritus following the administration of epidural narcotics is a very common and undesirable side effect. Therefore, we evaluated the use of a combination of naloxone and sufentanil via patient controlled epidural analgesia to determine if the incidence of pruritus was decreased when compared to the use of sufentanil alone. Methods: Patients scheduled for subtotal gastrectomy under general anesthesia were enrolled in a prospective, double-blinded and randomized trial. All patients received a $20{\mu}g$ epidural bolus of sufentanil in 5 ml of 0.2% ropivacaine. Following administration of the epidural, patients in the sufentanyl group (S) received a continuous epidural comprised of sufentanil ($0.75{\mu}g/ml$) in 0.2% ropivacaine, whereas patients in the naloxone group (N) received an epidural infusion comprised of naloxone ($4{\mu}g/ml$) and sufentanil ($0.75{\mu}g/ml$) in 0.2% ropivacaine. The infusion rate, demand dose and lockout interval were 5 ml/hr, 0.5 ml and 15 minutes respectively. Next, the occurrence of postoperative analgesia and side effects were evaluated by blinded observers. Results: The incidence of pruritus (47.4% versus 20.0%, P = 0.013) and nausea (42 .1 % versus 20.0%, P = 0.043) were lower in group N than in group S. In addition, there were no significant differences observed in the visual analogue scale, the incidence of vomiting or the incidence of sedation. Furthermore, epidural infusion of naloxone at $0.25-0.4{\mu}g/kg/hr$ did not affect the requirement for postoperative sufentanil. Conclusions: Epidural naloxone reduces epidural sufentanil induced pruritus and nausea without reversing its analgesic effects.

• The Korean Journal of Pharmacology
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• v.19 no.1
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• pp.115-122
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• 1983

The influences of diazepam and naloxone on the increase of plasma corticosterone level induced by morphine, pentazocine, ACTH, or picrotoxin were investigated in male mice. The results obtained were summarized as follows: 1) The increase induced by morphine or pentazocine of plasma corticosterone level was not affected by naloxone pretreatment but markedly suppressed by diazepam pretreatment. 2) The increase induced by ACTH of plasma corticosterone level was not affected by diazepam or naloxone pretreatment. 3) The picrotoxin markedly increased plasma corticosterone level, and the inceease was not affected by diazepam or naloxone pretreatment. This above results suggest that the increase induced by opioids of plasma corticosterone level seems to be rather related with other than opiate- or GABArerecptor.

• The Korean Journal of Nuclear Medicine
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• v.20 no.2
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• pp.79-84
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• 1986

The opiate antagonist, naloxone, was injected for the reversal of hypotension due to Korean hemorrhagic fever, and the authors observed changes in pituitary hormones. In the hypotensive phase of the Korean hemorrhagic fever, the f-endorphin was high, and normalized granually in the diuretic and convalescent period. The naloxone raised the pulse rate and the blood pressure within 30 minutes without change in the central venous pressure. Around 30 minuted after the injection of the naloxone, the $\beta-endorphin$, ACTH and cortisol rose. The prolactin fell down 60 minutes after the naloxone injection.

• The Journal of Korean Physical Therapy
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• v.8 no.1
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• pp.15-20
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• 1996

The purpose of this study were to 1) determine the analgesic effect of 632.8 nm of helium-neon (He-Ne) laser stimulation on acupuncture point in rat and 2) determine the reversal of analgesic effect by naloxone injection. Eighteen Sprague-Dawley rats were devided into three groups : control (n=6) : laser (n=6), laser stimulation at $3.58\;J/cm^2$ ; and naloxone (n=6), 1 mg/kg of naloxone chloride inject into peritoneum before laser stimulation at $3.63J/cm^2$. Tail-flick latency were measured pretreat and posttreat with hot plate $(55^{\circ}C)$. Data were analyzed using one-way ANOVA and paired t-teat for tail-flick latency. No significant change was noted in the tail-flick latency in either control or naloxone groups. But significant increased in tail-flick latency in taller group. The results suggest that He-Ne laser induced analgesic effect, and endogenous opioids may be involved in He-Ne laser induced analgesia.

• The Korean Journal of Pharmacology
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• v.25 no.1
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• pp.23-30
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• 1989

Buprenorphine, one of the mixed agonist-antagonist opioid drugs was used to inverstigate the opioid receptor on frog sciatic nerve A fibers. Action potentials were recorded for 4 hrs by a sucrose gap apparatus which were separated by four rubber membranes. To examine the one of the mechanism of action of buprenorphine, meperidine or naloxone was added after or before the treatment of buprenorphine. The results of this experiment were as follows: 1. Buprenorphine suppressed significantly the compound action potentials of frog sciatic nerve, and the maximal effects were shown both at $10^{-4}\;M$ and at $10^{-8}\;M$. 2. The dose-response relationship of buprenorphine on the depressant effect in frog sciatic nerve was biphasic and inverted U-shaped. 3. Buprenorphine blocked the effect of Meperidine $(10^{-3}\;M)$ on this preparation. 4. The depressant effcct of Buprenorphine on frog sciatic nerve was blocked by $10^{-8}\;M$ naloxone. From the above results, buprenorphine acts as one of agoinist-antagonistic effect on frog sciatic nerve, and the opioid receptor on this preparation is located on or near the intracellular opening of the sodium channels, which are sensitive to naloxone.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.67-72
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• 2014

To investigate the alteration of c-Jun N-terminal kinase (JNK) activity after myocardial ischemia reperfusion injury (MIRI) and further explore the effect of naloxone postconditioning on MIRI. Forty male Sprague Dawley rats were randomly divided into five groups: sham operation (sham, n=8); ischemia reperfusion (IR, n=8); IR+naloxone 0.5 mg/kg (Nal L, n=8); IR+naloxone 1.0 mg/kg (Nal M, n=8); IR+naloxone 2.0 mg/kg (Nal H, n=8). Pathological changes of myocardial tissue were visualized by HE staining. The expression of p-JNK, and the apoptosis of cardiomyocytes were investigated with Western blotting and the TUNEL assay, respectively. Irregular arrangement and aberrant structure of myocardial fibers, cardiomyocytes with granular or vacuolar degeneration, and inflammatory cells infiltrating the myocardial interstitial regions characterized MIRI in the IR group. Signs of myocardial injury and inflammatory infiltration were less prominent in the Nal-treated groups. The expression of p-JNK in the sham group and in all Nal-treated groups was significantly lower than that in the IR group (p<0.01). The apoptosis index of cardiomyocytes in the IR group was significantly higher than in the sham group (p<0.01). The apoptosis indices of cardiomyocytes in all Nal-treated groups were significantly reduced to 55.4%, 26.2%, and 27.6%, respectively, of the IR group (p<0.01). This study revealed that Naloxone postconditioning before reperfusion inhibits p-JNK expression and decreases cell apoptosis, thus alleviating MIRI.

• The Korean Journal of Pharmacology
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• v.19 no.2
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• pp.57-67
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• 1983

The influence of electrolyte concentrations on the action of morphine and naloxone was studied in the myenteric plexus-longitudinal muscle preparation of guinea-pig ileum to examine whether opiate receptor binding obseved in vitro with homogenates represents binding to the pharmacological receptor. The preparations were suspended in a modified Krebs-Henseleit bicarbonate buffer solution and electrically stimulated at 0.2 Hz. Morphine inhibited electrically evoked contractions; the concentration of morphine required for a 50-percent inhibition was 190 nM. This inhibitory action of morphine was potentiated in a medium containing lower concentrations of : $Na^+\;or\;K^+$, or by the addition of $Mn^{2+}$ to the medium, and weakened by increasing the concentration of $Ca^{2+}$ or decreasing the concentration of $Mg^{2+}$. Naloxone antagonized these actions of morphine: however, $pA_2values$ for naloxone (indices of affinity for antagonists, approximately 8.8) were unaffected by these electrolyte concentrations. Thus, changes in the inhibitory action of morphine caused by alterations in electrolyte concentrations are probably not the result of changes in the affinity of the receptor for opiates, but due to alterations in the events which precede or follow the receptor binding. Effects of electrolytes on the affinity of the functional opiate receptor for naloxone in guinea-pig ileum are apparently different from those reported with the specific binding sites for opiates in brain homogenate.

• Journal of Ginseng Research
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• v.13 no.2
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• pp.239-241
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• 1989

Naloxone partially antagonized the analgesic effect of a large dose of morphine and inhibited the development of an acute type tolerance. Ginseng total saponins did not antagonize the analgesia of a large dose of morphine but inhibited the delrelopment of acute and delayed types tolerance. The morphine analgesia and the development of acute type tolerance were affected by the opioid receptor antagonist, naloxone, but the development of acute type tolerance was not. Ginseng total saponins partially inhibited the development of the delayed type tolerance that was not inhibited by naloxone, but also partially suppressed the development of the acute type tolerance that was completely inhibited by naloxone. These results imply that the partial inhibition of the development of the acute and delayed types tolerance by ginseng total saponins is not mediated by the opioid receptors.

• Journal of Pharmaceutical Investigation
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• v.25 no.2
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• pp.117-123
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• 1995

For the effective administration of narcotic antagonist, the application of sustained release implantable systems with biodegradable polyphosphazene was examined. Using poly[(diethyl glutamate)-co-(ethyl glycinate) phosphazene], the implantable devices containing naloxone hydrochloride were prepared and in vivo implantation studies were carried out subcutaneously in rat and rabbit with this preparation for the biocompatibility and pharmacokinetics. The histological finding in rats at initial time period was the inflammation that occurred focally around the implants, but they were showed subsequent mild and limited chronic inflammations and the irreversible changes such as necrosis and degeneration of the muscle or connective tissues were not observed. Therefore the placebo and naloxone implants are considered to be biocompatible formulations histologically. In pharmacokinetic studies, the release of naloxone from the naloxone implants into blood plasma was maintained in 192 hours, but the initial burst effect was observed. If this problem was solved, the application for the narcotic antagonist sustained release systems can be expected.