The opioid epidemic in the United States continues to take the lives of many individuals, with overdoses continuing to rise every year. Naloxone is an opioid antagonist that is efficacious in temporarily reversing opi...The opioid epidemic in the United States continues to take the lives of many individuals, with overdoses continuing to rise every year. Naloxone is an opioid antagonist that is efficacious in temporarily reversing opioid overdoses. Pharmacists play an important role in the accessibility and education of naloxone in both the community and health system settings. Recent efforts, such as co-dispensing naloxone with opioid prescriptions, naloxone training programs, and approval of naloxone to be over-the-counter, have been implemented in hopes to better control the opioid epidemic. Despite the efforts to make naloxone more accessible, there are still some barriers to overcome such as lack of training, cost, stigma, and patient refusal. This review aims to explore the contributions pharmacists have made thus far and define the barriers that still have to be resolved.展开更多
Summary： To investigate the effect of preceding naloxone injection into the third cerebroventricle or acute subdiaphragmatic vagotomy on the gastric acid secretion inhibited by the somatostatin analogue octreotide gi...Summary： To investigate the effect of preceding naloxone injection into the third cerebroventricle or acute subdiaphragmatic vagotomy on the gastric acid secretion inhibited by the somatostatin analogue octreotide given by intracerebroventricular （icv） injection. The third ventricles were cannulated in male Wistar rats anesthetized with sodium pentobarbital. One week later, acute gastric lumen perfusion was carried out. The gastric perfusion samples were collected every 10 min and were titrated by 0.01 mol/L NaOH to neuter. On the basis of subcutaneous injection of pentagastrin （G-5, 160 g/kg）, icv injection of physiological saline （group A, n=20）, icv injection of octreotide （0.05 μ g） （group B, n=20）, icv injection of naloxone （2.5 μ g）＋octreotide （0.05 μg） （group C, n=20）, acute subdiaphragmatic vagotomy＋ icv injection of physiological saline （group D, n=20）, or acute subdia- phragrnatic vagotomy＋icv injection of octreotide （0.05 μg） （group E, n=20） were conducted. Before and after icv injection, 1-h total acid output （TAO） was determined and compared. The experimental data were expressed in change rate （%） of TAO. The change rates （%） of TAO were 4.60 % in group A, -20.35 % in group B, - 18.06 % in group C, 5.01% in group D and -21.59 % in group E, respectively. Comparison of group B or C versus group A showed that P〈0.01 and comparison between the group E versus group D showed that P〈0.01. Whereas the differences between group C and group B, group E and group B were not statistically significant （P〉0.05 for all）. The results indicate that the central inhibition of gastric acid secretion by octreotide may not be mediated by the endogenous opi- ate substance or its receptor and the peripheral pathway for icv injection of octreotide to suppress gastric acid secretion is via extra-vagus route.展开更多
Background: Controlled-release oxycodone/naloxone(OXN-CR) maintains the effect of opioid-induced analgesia through oxycodone while reducing the occurrence rate of opioid-induced constipation through naloxone. The pres...Background: Controlled-release oxycodone/naloxone(OXN-CR) maintains the effect of opioid-induced analgesia through oxycodone while reducing the occurrence rate of opioid-induced constipation through naloxone. The present study was designed to assess the non-inferiority of OXN-CR to controlled-release oxycodone(OX-CR) for the control of cancer-related pain in Korean patients.Methods: In this randomized, open-labeled, parallel-group, phase IV study, we enrolled patients aged 20 years or older with moderate to severe cancer-related pain [numeric rating scale(NRS) pain score ≥4] from seven Korean oncology/hematology centers. Patients in the intention-to-treat(ITT) population were randomized(1:1) to OXNCR or OX-CR groups. OXN-CR was administered starting at 20 mg/10 mg per day and up-titrated to a maximum of80 mg/40 mg per day for 4 weeks, and OX-CR was administered starting at 20 mg/day and up-titrated to a maximum of 80 mg/day for 4 weeks.The primary efficacy endpoint was the change in NRS pain score from baseline to week4, with non-inferiority margin of-1.5. Secondary endpoints included analgesic rescue medication intake, patientreported change in bowel habits, laxative intake, quality of life(QoL), and safety assessments.Results: Of the ITT population comprising 128 patients, 7 with missing primary efficacy data and 4 who violated the eligibility criteria were excluded from the efficacy analysis. At week 4, the mean change in NRS pain scores was not significantly different between the OXN-CR group(n = 58) and the OX-CR group(n = 59)(-1.586 vs.-1.559,P = 0.948). The lower limit of the one-sided 95% confidence interval(-0.776 to 0.830) for the difference exceeded the non-inferiority margin(P < 0.001). The OXN-CR and OX-CR groups did not differ significantly in terms of analgesic rescue medication intake, change in bowel habits, laxative intake, QoL, and safety assessments.Conclusions: OXN-CR was non-inferior to OX-CR in terms of pain reduction after 4 weeks of treatment and had a similar safety profile. Studies in larger populations of Korean patients with cancer-related pain are needed to further investigate the effectiveness of OXN-CR for long-term pain control and constipation alleviation.Trial registration ClinicalTrials.gov NCT01313780, registered March 8。展开更多
The effect of morphine and naloxone on release of the excitatory amino acids (EAAs) of spinal astrocytes induced by TNF-α was studied. Astrocytes were purified from 2- to 3-day old SD rats and divided into 8 groups: ...The effect of morphine and naloxone on release of the excitatory amino acids (EAAs) of spinal astrocytes induced by TNF-α was studied. Astrocytes were purified from 2- to 3-day old SD rats and divided into 8 groups: group 1 (without any stimulatants); group 2 (10 ng/ml TNF-α); group3 (10 ng/ml TNF-α+0.5 μmol/L morphine); group 4 (10 ng/ml TNF-α+1.0 μmol/L morphine); group 5 (10 ng/ml TNF-α+2.0 μmol/L morphine); group 6 (10 ng/ml TNF-α+0.5 μmol/L naloxone); group 7 (10 ng/ml TNF-α+1.0 μmol/L naloxone); group 8 (10 ng/ml TNF-α+2.0 μmol/L naloxone). In group 2, 3, 4 and 5, 0, 0.5, 1.0 or 2.0 μmol/L morphine was added to the cells cultured with serum-free Neurobasal/B27 medium containing 10 ng/ml TNF-α respectively, while in group 6, 7 and 8, 0.5, 1.0 or 2.0 μmol/L naloxone was added respectively to the cells cultured with serum-free Neurobasal/B27 medium containing 10 ng/ml TNF-α. After 30 min incubation, high-pressure liquid chromatography (HPLC) was used to measure the levels of EAAs in all cultured cells. The results showed the level of EAAs in group 2 was significant higher than in group 1 (P<0.01). As compared with group 2, the levels of EAAs in group 3, 4 and 5 were decreased with the difference being significant between group 5 and group 2 (P<0.01) or between group 4 and group 2 (P<0.05). The levels of EAAs in group 6, 7 and group 8 was significantly lower than in group 2 (P<0.05 or P<0.01). It was concluded that TNF-α could promote the release of glutamate and aspartate from astrocytes, and morphine and naloxone might reduce the release of EAAs in cultured spinal astrocytes induced by TNF-α.展开更多
β-endorphin is the most actively endogenous substance of cerebral endorphin. When combined with opiate receptor specially, it manifests a strong morphine-like activity and can decrease sensitivity of central nervous ...β-endorphin is the most actively endogenous substance of cerebral endorphin. When combined with opiate receptor specially, it manifests a strong morphine-like activity and can decrease sensitivity of central nervous system to carbon dioxide so as to inhibit breath. OBJECTIVE： To observe the changes of content of plasma β-endorphin in neonates with severe asphyxia after naloxone treatment in a large dosage. DESIGN： Randomized controlled observation. SETTINGS： Department of Pediatrics, Shenzhen Shajing People＇s Hospital; Center of Pediatrics, Guangzhou Zhujiang Hospital. PARTICIPANTS： A total of 97 neonates with severe asphyxia including 57 boys and 40 girls were selected from Neonatal Intensive Care Unit, Department of Pediatrics, Shenzhen Shajing People＇s Hospital from January 2004 to November 2005. Their gestational age was （38±3） weeks, body mass was （3.2±1.7） kg, and hospitalization duration was （2.8±2.3） hours. All neonates met the diagnostic criteria of with severe asphyxia and all their parents provided the confirmed consent. METHODS： All neonates were treated with inspired oxygen, sedation, stopping terror, decreasing cranial pressure, maintaining a well blood perfusion and normal level of blood glucose （about 5.0 retool/L）. After hospitalization, 0.1 mg/（kg·d） naloxone hydrochloride （Beijing Sihuan Pharmaceutical Technology Co., Ltd.; certification： HI0900021; bullet preparation; 0.4 mg/ampoule） was intravenously dribbled into neonates for 4 - 6 hours, 14 days in total. 2 mL blood was collected from radial artery in neonates at the beginning of hospitalization and at 3 days after naloxone treatment, put in aprotinin-pre-cool tube, mixed evenly, and centrifuged at hypothermia. Plasma was maintained in refrigerator at - 70 ℃. The kit was provided by Neurobiology Department of Shanghai Second Military Medical University of Chinese PLA. Concentration of plasma β-endorphin was measured by using radio-immunity assay.All data were expressed as Mean ± SD and results were compared with paired t test. MAIN OUTCOME MEASURE： Concentration of plasma β-endorphin. RESULTS： All 97 neonates were involved in the final analysis. Concentration of plasma β-endorphin in neonates with severe asphyxia was lower after treatment as compared with that before treatment, and there was significant difference （t = 10.31, P 〈 0.01 ）. CONCLUSION： Naloxone can decrease level of plasma β-endorphin in neonates with severe asphyxia.展开更多
Stimulating SmI cortex like needling points produced analgesic effect in rats.Under the background of ventrical microinjecting atropine（10μg/2μl）or naloxone（20μg/20μl）tailflick latency（TEL）remained unchanged...Stimulating SmI cortex like needling points produced analgesic effect in rats.Under the background of ventrical microinjecting atropine（10μg/2μl）or naloxone（20μg/20μl）tailflick latency（TEL）remained unchanged after stimulating SmI.Comparing atropine group or naloxone group with normal saline group it was shown that there were a statistical difference in TFL between the two groups respectively.Thus,both ACh and endogenous morphine-like factors may participate in analgesic effect as a neurotransmitter of the corticofugal modulation of pain.展开更多
5-HT content in medulla oblongata plus pons and DA level in brain stem obviously increased,while NA concentration in telencephalon markedly decreased in EAA.A previous injection ofnaloxone,a blocker of opiate receptor...5-HT content in medulla oblongata plus pons and DA level in brain stem obviously increased,while NA concentration in telencephalon markedly decreased in EAA.A previous injection ofnaloxone,a blocker of opiate receptor,could partially inhibit the EAA,abolish the effects ofEA’s increasing the 5-HT content in the medulla oblongata plus pons and the DA level in thebrain stem,and decrease the NA level in the diencephalon after EA.These results indicate thatEA may mediate the metabolism of the central monoamine neurotransmitters partially via opiatereceptor to exert its analgesic effect.展开更多
BACKGROUND： Ephedrine promotes neural plasticity in rats following cerebral ischemia/reperfusion injury. Ephedrine has been combined with naloxone in some studies, and it has been confirmed that their combination has...BACKGROUND： Ephedrine promotes neural plasticity in rats following cerebral ischemia/reperfusion injury. Ephedrine has been combined with naloxone in some studies, and it has been confirmed that their combination has synergistic effects on increasing neural plasticity following cerebral ischemia/reperfusion injury. OBJECTIVE： To investigate the effects of ephedrine combined with various doses of naloxone on neural plasticity and to find an optimal dose of naloxone in rats after cerebral ischemia/reperfusion injury by analyzing growth associated protein-43 （GAP-43）, synaptophysin and β-endorphin expression in the hippocampal CA3 area. DESIGN, TIME AND SETTING： This immunohistochemical, randomized, controlled, animal experiment was performed at the Chongqing Research Institute of Pediatrics, China from September 2007 to June 2008. MATERIALS： Ephedrine hydrochloride injection and naloxone hydrochloride injection were respectively purchased from Shandong Lvliang Pharmaceutical Factory, China and Sichuan Jingwei Pharmaceutical Co., Ltd., China. A total of 192 healthy adult Sprague Dawley rats were used to establish models of left middle cerebral artery occlusion using the suture occlusion method. METHODS： At 2 hours following cerebral ischemia, the rats were intraperitoneally injected with 1.5 mg/kg/d ephedrine （ephedrine group）, with 0.1, 0.2, or 0.3 mg/kg/d naloxone （low, moderate and high doses of naloxone groups）, with 1.5 mg/kg/d ephedrine ＋ 0.1, 0.2, or 0.3 mg/kg/d naloxone （ephedrine ＋ low, moderate and high doses of naloxone groups）, and with 0.5 mL saline （model group）, respectively. MAIN OUTCOME MEASURES： GAP-43, synaptophysin and β -endorphin expression were detected in the hippocampal CA3 area using immunohistochemistry 1-4 weeks after surgery. Sensorimotor integration in rats was assessed using the beam walking test. RESULTS： GAP-43 and synaptophysin expression was greater in the ephedrine group, and in the ephedrine ＋ moderate and high doses of naloxone groups compared with the model group. GAP-43 and synaptophysin expression was greatest in the ephedrine ＋ high dose of naloxone group at 2 and 3 weeks alter surgery. β -endorphin expression was significantly lower in the ephedrine group, and in the ephedrine ＋ moderate and high doses of naloxone groups compared with the model group （P 〈 0.05）. β -endorphin expression was persistently low in the ephedrine ＋ high dose of naloxone group. At 1-3 weeks after surgery, the beam walking test score was significantly higher in the ephedrine group and ephedrine ＋ various doses of naloxone groups than in the model group （P 〈 0.05）. The score was higher in the ephedrine ＋ moderate and high doses of naloxone groups than in the ephedrine group （P 〈 0.05）. Moreover, the score was increased as the dose of naloxone increased in the ephedrine ＋ various doses of naloxone groups. CONCLUSION： Ephedrine promotes GAP-43 and synaptophysin expression, inhibits /3 -endorphin expression in the hippocampal CA3 area, and improves motor function in rats following cerebral ischemia/reperfusion injury. Naloxone does not have the above-mentioned effects. During combined treatment with ephedrine and naloxone, however, the above-described effects are enhanced with an increased dose of naloxone. The combination of ephedrine （1.5 mg/kg/d） and naloxone （0.3 mg/kg/d） can produce optimal therapeutic efficacy in treatment of cerebral ischemic injury.展开更多
文摘The opioid epidemic in the United States continues to take the lives of many individuals, with overdoses continuing to rise every year. Naloxone is an opioid antagonist that is efficacious in temporarily reversing opioid overdoses. Pharmacists play an important role in the accessibility and education of naloxone in both the community and health system settings. Recent efforts, such as co-dispensing naloxone with opioid prescriptions, naloxone training programs, and approval of naloxone to be over-the-counter, have been implemented in hopes to better control the opioid epidemic. Despite the efforts to make naloxone more accessible, there are still some barriers to overcome such as lack of training, cost, stigma, and patient refusal. This review aims to explore the contributions pharmacists have made thus far and define the barriers that still have to be resolved.
基金This work was supported by Returning Overseas Scholar Science Study Foundation, the Education Ministry of China (No. 2005383)
文摘Summary： To investigate the effect of preceding naloxone injection into the third cerebroventricle or acute subdiaphragmatic vagotomy on the gastric acid secretion inhibited by the somatostatin analogue octreotide given by intracerebroventricular （icv） injection. The third ventricles were cannulated in male Wistar rats anesthetized with sodium pentobarbital. One week later, acute gastric lumen perfusion was carried out. The gastric perfusion samples were collected every 10 min and were titrated by 0.01 mol/L NaOH to neuter. On the basis of subcutaneous injection of pentagastrin （G-5, 160 g/kg）, icv injection of physiological saline （group A, n=20）, icv injection of octreotide （0.05 μ g） （group B, n=20）, icv injection of naloxone （2.5 μ g）＋octreotide （0.05 μg） （group C, n=20）, acute subdiaphragmatic vagotomy＋ icv injection of physiological saline （group D, n=20）, or acute subdia- phragrnatic vagotomy＋icv injection of octreotide （0.05 μg） （group E, n=20） were conducted. Before and after icv injection, 1-h total acid output （TAO） was determined and compared. The experimental data were expressed in change rate （%） of TAO. The change rates （%） of TAO were 4.60 % in group A, -20.35 % in group B, - 18.06 % in group C, 5.01% in group D and -21.59 % in group E, respectively. Comparison of group B or C versus group A showed that P〈0.01 and comparison between the group E versus group D showed that P〈0.01. Whereas the differences between group C and group B, group E and group B were not statistically significant （P〉0.05 for all）. The results indicate that the central inhibition of gastric acid secretion by octreotide may not be mediated by the endogenous opi- ate substance or its receptor and the peripheral pathway for icv injection of octreotide to suppress gastric acid secretion is via extra-vagus route.
文摘Background: Controlled-release oxycodone/naloxone(OXN-CR) maintains the effect of opioid-induced analgesia through oxycodone while reducing the occurrence rate of opioid-induced constipation through naloxone. The present study was designed to assess the non-inferiority of OXN-CR to controlled-release oxycodone(OX-CR) for the control of cancer-related pain in Korean patients.Methods: In this randomized, open-labeled, parallel-group, phase IV study, we enrolled patients aged 20 years or older with moderate to severe cancer-related pain [numeric rating scale(NRS) pain score ≥4] from seven Korean oncology/hematology centers. Patients in the intention-to-treat(ITT) population were randomized(1:1) to OXNCR or OX-CR groups. OXN-CR was administered starting at 20 mg/10 mg per day and up-titrated to a maximum of80 mg/40 mg per day for 4 weeks, and OX-CR was administered starting at 20 mg/day and up-titrated to a maximum of 80 mg/day for 4 weeks.The primary efficacy endpoint was the change in NRS pain score from baseline to week4, with non-inferiority margin of-1.5. Secondary endpoints included analgesic rescue medication intake, patientreported change in bowel habits, laxative intake, quality of life(QoL), and safety assessments.Results: Of the ITT population comprising 128 patients, 7 with missing primary efficacy data and 4 who violated the eligibility criteria were excluded from the efficacy analysis. At week 4, the mean change in NRS pain scores was not significantly different between the OXN-CR group(n = 58) and the OX-CR group(n = 59)(-1.586 vs.-1.559,P = 0.948). The lower limit of the one-sided 95% confidence interval(-0.776 to 0.830) for the difference exceeded the non-inferiority margin(P < 0.001). The OXN-CR and OX-CR groups did not differ significantly in terms of analgesic rescue medication intake, change in bowel habits, laxative intake, QoL, and safety assessments.Conclusions: OXN-CR was non-inferior to OX-CR in terms of pain reduction after 4 weeks of treatment and had a similar safety profile. Studies in larger populations of Korean patients with cancer-related pain are needed to further investigate the effectiveness of OXN-CR for long-term pain control and constipation alleviation.Trial registration ClinicalTrials.gov NCT01313780, registered March 8。
文摘The effect of morphine and naloxone on release of the excitatory amino acids (EAAs) of spinal astrocytes induced by TNF-α was studied. Astrocytes were purified from 2- to 3-day old SD rats and divided into 8 groups: group 1 (without any stimulatants); group 2 (10 ng/ml TNF-α); group3 (10 ng/ml TNF-α+0.5 μmol/L morphine); group 4 (10 ng/ml TNF-α+1.0 μmol/L morphine); group 5 (10 ng/ml TNF-α+2.0 μmol/L morphine); group 6 (10 ng/ml TNF-α+0.5 μmol/L naloxone); group 7 (10 ng/ml TNF-α+1.0 μmol/L naloxone); group 8 (10 ng/ml TNF-α+2.0 μmol/L naloxone). In group 2, 3, 4 and 5, 0, 0.5, 1.0 or 2.0 μmol/L morphine was added to the cells cultured with serum-free Neurobasal/B27 medium containing 10 ng/ml TNF-α respectively, while in group 6, 7 and 8, 0.5, 1.0 or 2.0 μmol/L naloxone was added respectively to the cells cultured with serum-free Neurobasal/B27 medium containing 10 ng/ml TNF-α. After 30 min incubation, high-pressure liquid chromatography (HPLC) was used to measure the levels of EAAs in all cultured cells. The results showed the level of EAAs in group 2 was significant higher than in group 1 (P<0.01). As compared with group 2, the levels of EAAs in group 3, 4 and 5 were decreased with the difference being significant between group 5 and group 2 (P<0.01) or between group 4 and group 2 (P<0.05). The levels of EAAs in group 6, 7 and group 8 was significantly lower than in group 2 (P<0.05 or P<0.01). It was concluded that TNF-α could promote the release of glutamate and aspartate from astrocytes, and morphine and naloxone might reduce the release of EAAs in cultured spinal astrocytes induced by TNF-α.
文摘β-endorphin is the most actively endogenous substance of cerebral endorphin. When combined with opiate receptor specially, it manifests a strong morphine-like activity and can decrease sensitivity of central nervous system to carbon dioxide so as to inhibit breath. OBJECTIVE： To observe the changes of content of plasma β-endorphin in neonates with severe asphyxia after naloxone treatment in a large dosage. DESIGN： Randomized controlled observation. SETTINGS： Department of Pediatrics, Shenzhen Shajing People＇s Hospital; Center of Pediatrics, Guangzhou Zhujiang Hospital. PARTICIPANTS： A total of 97 neonates with severe asphyxia including 57 boys and 40 girls were selected from Neonatal Intensive Care Unit, Department of Pediatrics, Shenzhen Shajing People＇s Hospital from January 2004 to November 2005. Their gestational age was （38±3） weeks, body mass was （3.2±1.7） kg, and hospitalization duration was （2.8±2.3） hours. All neonates met the diagnostic criteria of with severe asphyxia and all their parents provided the confirmed consent. METHODS： All neonates were treated with inspired oxygen, sedation, stopping terror, decreasing cranial pressure, maintaining a well blood perfusion and normal level of blood glucose （about 5.0 retool/L）. After hospitalization, 0.1 mg/（kg·d） naloxone hydrochloride （Beijing Sihuan Pharmaceutical Technology Co., Ltd.; certification： HI0900021; bullet preparation; 0.4 mg/ampoule） was intravenously dribbled into neonates for 4 - 6 hours, 14 days in total. 2 mL blood was collected from radial artery in neonates at the beginning of hospitalization and at 3 days after naloxone treatment, put in aprotinin-pre-cool tube, mixed evenly, and centrifuged at hypothermia. Plasma was maintained in refrigerator at - 70 ℃. The kit was provided by Neurobiology Department of Shanghai Second Military Medical University of Chinese PLA. Concentration of plasma β-endorphin was measured by using radio-immunity assay.All data were expressed as Mean ± SD and results were compared with paired t test. MAIN OUTCOME MEASURE： Concentration of plasma β-endorphin. RESULTS： All 97 neonates were involved in the final analysis. Concentration of plasma β-endorphin in neonates with severe asphyxia was lower after treatment as compared with that before treatment, and there was significant difference （t = 10.31, P 〈 0.01 ）. CONCLUSION： Naloxone can decrease level of plasma β-endorphin in neonates with severe asphyxia.
文摘Stimulating SmI cortex like needling points produced analgesic effect in rats.Under the background of ventrical microinjecting atropine（10μg/2μl）or naloxone（20μg/20μl）tailflick latency（TEL）remained unchanged after stimulating SmI.Comparing atropine group or naloxone group with normal saline group it was shown that there were a statistical difference in TFL between the two groups respectively.Thus,both ACh and endogenous morphine-like factors may participate in analgesic effect as a neurotransmitter of the corticofugal modulation of pain.
文摘5-HT content in medulla oblongata plus pons and DA level in brain stem obviously increased,while NA concentration in telencephalon markedly decreased in EAA.A previous injection ofnaloxone,a blocker of opiate receptor,could partially inhibit the EAA,abolish the effects ofEA’s increasing the 5-HT content in the medulla oblongata plus pons and the DA level in thebrain stem,and decrease the NA level in the diencephalon after EA.These results indicate thatEA may mediate the metabolism of the central monoamine neurotransmitters partially via opiatereceptor to exert its analgesic effect.
基金a grant from the Bureau of Health of Chongqing City, No. [2007]1(07-2-153)
文摘BACKGROUND： Ephedrine promotes neural plasticity in rats following cerebral ischemia/reperfusion injury. Ephedrine has been combined with naloxone in some studies, and it has been confirmed that their combination has synergistic effects on increasing neural plasticity following cerebral ischemia/reperfusion injury. OBJECTIVE： To investigate the effects of ephedrine combined with various doses of naloxone on neural plasticity and to find an optimal dose of naloxone in rats after cerebral ischemia/reperfusion injury by analyzing growth associated protein-43 （GAP-43）, synaptophysin and β-endorphin expression in the hippocampal CA3 area. DESIGN, TIME AND SETTING： This immunohistochemical, randomized, controlled, animal experiment was performed at the Chongqing Research Institute of Pediatrics, China from September 2007 to June 2008. MATERIALS： Ephedrine hydrochloride injection and naloxone hydrochloride injection were respectively purchased from Shandong Lvliang Pharmaceutical Factory, China and Sichuan Jingwei Pharmaceutical Co., Ltd., China. A total of 192 healthy adult Sprague Dawley rats were used to establish models of left middle cerebral artery occlusion using the suture occlusion method. METHODS： At 2 hours following cerebral ischemia, the rats were intraperitoneally injected with 1.5 mg/kg/d ephedrine （ephedrine group）, with 0.1, 0.2, or 0.3 mg/kg/d naloxone （low, moderate and high doses of naloxone groups）, with 1.5 mg/kg/d ephedrine ＋ 0.1, 0.2, or 0.3 mg/kg/d naloxone （ephedrine ＋ low, moderate and high doses of naloxone groups）, and with 0.5 mL saline （model group）, respectively. MAIN OUTCOME MEASURES： GAP-43, synaptophysin and β -endorphin expression were detected in the hippocampal CA3 area using immunohistochemistry 1-4 weeks after surgery. Sensorimotor integration in rats was assessed using the beam walking test. RESULTS： GAP-43 and synaptophysin expression was greater in the ephedrine group, and in the ephedrine ＋ moderate and high doses of naloxone groups compared with the model group. GAP-43 and synaptophysin expression was greatest in the ephedrine ＋ high dose of naloxone group at 2 and 3 weeks alter surgery. β -endorphin expression was significantly lower in the ephedrine group, and in the ephedrine ＋ moderate and high doses of naloxone groups compared with the model group （P 〈 0.05）. β -endorphin expression was persistently low in the ephedrine ＋ high dose of naloxone group. At 1-3 weeks after surgery, the beam walking test score was significantly higher in the ephedrine group and ephedrine ＋ various doses of naloxone groups than in the model group （P 〈 0.05）. The score was higher in the ephedrine ＋ moderate and high doses of naloxone groups than in the ephedrine group （P 〈 0.05）. Moreover, the score was increased as the dose of naloxone increased in the ephedrine ＋ various doses of naloxone groups. CONCLUSION： Ephedrine promotes GAP-43 and synaptophysin expression, inhibits /3 -endorphin expression in the hippocampal CA3 area, and improves motor function in rats following cerebral ischemia/reperfusion injury. Naloxone does not have the above-mentioned effects. During combined treatment with ephedrine and naloxone, however, the above-described effects are enhanced with an increased dose of naloxone. The combination of ephedrine （1.5 mg/kg/d） and naloxone （0.3 mg/kg/d） can produce optimal therapeutic efficacy in treatment of cerebral ischemic injury.
