Objective To investigate the analgesia induced by receptin （REC）, a chemically modified cobratoxin （CTX, a long-chain postsynaptic α-neurotoxin from Thailand cobra venom）, and the effects of atropine and naloxone...Objective To investigate the analgesia induced by receptin （REC）, a chemically modified cobratoxin （CTX, a long-chain postsynaptic α-neurotoxin from Thailand cobra venom）, and the effects of atropine and naloxone on antinociceptive activity of REC in rodent pain models. Methods REC was administered intraperitoneally （5 mg/kg, 7.07 mg/kg, or 10 mg/kg, i.p.） or intra-cerebral venticularly （62.5 μg/kg, i.c.v.）. The antinociceptive action was determined using the hotlate test, the acetic acid writhing test and tail flick assay in mice and rats. The involvement of cholinergic and the opioid peptidergic systems in REC-induced analgesia were examined by pretreatment of animals with atropine （Atr; 0.5 mg/kg, i.m. or 10 mg/kg, i.p.） or naloxone （Nal; 3 mg/kg, i.p.）. The effect of REC on motor activity was tested using the Animex test in mice. Results REC （5 mg/kg, 7.07 mg/kg or 10 mg/kg, i.p.） exhibited a dose-dependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. The significant analgesia of REC was seen 2 h to 3 h after its administration. In the rat-tail flick assay, the administration of REC at 62.5 μg/kg （1/160 of systemic dose; i.c.v.）produced marked analgesic effects. Atropine at 0.5 mg/kg （i.m.）, 10 mg/kg （i.p.） or naloxone at 3 mg/kg （i.p.） failed to block the analgesic effects of REC. REC at the highest effective dose of 10 mg/kg did not change the spontaneous mobility of mice. Conclusion These results demonstrate that REC has analgesic effect. This activity appears to be mediated through the peripheral nervous system though central nervous system may contribute to REC＇s analgesic effects. The central cholinergic system and opioid peptidergic system appear not to be involved in the antinociceptive action of REC.展开更多
The pharmacokinetics and absolute bioavailability of the sublingual naloxone tablet were studied with HPLC-electrochemical detection. Eight male dogs received single 5 mg dose of naloxone intravenously, the plasma con...The pharmacokinetics and absolute bioavailability of the sublingual naloxone tablet were studied with HPLC-electrochemical detection. Eight male dogs received single 5 mg dose of naloxone intravenously, the plasma concentration-time curves could be fitted to two-compartment open model, with 12.0 min of t1/2( , 143.4 min of t1/2( and 7.92 mg(min/L of AUC. The same eight dogs received 5 mg dose of the sublingual naloxone tablet after an interval of a week. The main pharmacokinetic parameters were: t1/2ka = 11.0 min, t1/2( = 15.4 min, t1/2( = 164.1 min, Tmax = 27.7 min, Cmax = 34.2 ng / ml, and AUC = 6.79 mg(min / L, respectively. The plasma concentration-time curves were fitted to the first order absorption two-compartment open model also. The mean absolute bioavailability of the sublingual naloxone tablet was 86.8 ( 10.9%. No statistically significant differences were found with t1/2(, t1/2(, ( and ( between the two routes of administration. These results indicated that the course of disposition for naloxone in dogs was similar for the two routes of administration, and the absolute bioavailability of the sublingual naloxone tablet was high. Thus satisfactory clinical effects could be expected.展开更多
I read with great interest the recent article by Chen et al in a recent issue of your esteemed journal.The article is highly thought provoking.One emerging therapeutic alternative for opioid induced constipation is th...I read with great interest the recent article by Chen et al in a recent issue of your esteemed journal.The article is highly thought provoking.One emerging therapeutic alternative for opioid induced constipation is the emergence of opioid/naloxone prolonged release combinations.For instance,naloxone when administered in a 1:2 ratio with oxycodone reverses the inhibitory effect of oxycodone on the gastrointestinal tract.The advantage of oxycodone/naloxone prolonged release(OXN) is that while its anti-nociceptive efficacy is equivalent to that of oxycodone prolonged release(OXC),it significantly decreases the "Bowel Function Index" thereby ameliorating symptoms of opioid induced constipation to a large extent.Schutter et al in a recent study have reported a decrease in the bowel function index from 38.2 to 15.1.Similarly,L wenstein et al in another recent study have reported that following a month of therapy,complete spontaneous bowel movements per week is increased from one in OXC therapy to three in OXN therapy.展开更多
Naloxone is a well-known opioid antagonist indicated for the treatment of CNS （central nervous system） and respiratory depression induced by natural or synthetic opioid in adults and neonates whose mothers have rece...Naloxone is a well-known opioid antagonist indicated for the treatment of CNS （central nervous system） and respiratory depression induced by natural or synthetic opioid in adults and neonates whose mothers have received opioids. While it has been reported that an injection of 0.2 mg/mL of naloxone hydrochloride is physically and chemically stable, data on photostability on continuous i.v. infusion of 0.2 mg/mL of naloxone hydrochloride has not been reported. Therefore, a method was required for assessment of naloxone hydrochloride photostability. A high performance LC-MS （liquid chromatography/mass spectrometry） method was established to evaluate the photostability of naloxone hydrochloride. Injections of naloxone hydrochloride in 0.9% sodium chloride were exposed to artificial light and stored at room temperature （22 ~C） and 37 ~C. Naloxone losses up to 9.79% of its initial concentration when exposed to light at room temperature for 192 h, but the degradation increased up to 14.91% as the storage temperature increase. The disappearance of naloxone hydrochloride was correlated with the appearance of nor-oxymorphonedegradant. Naloxone hydrochloride is photosensitive and degradation increased at highly temperature and light intensity. Therefore, naloxone i.v. infusion solutions should either be protected from light and/or be frequently replaced when being administered to patients.展开更多
Objective To observe the efficacy of acupuncture combined with naloxone hydrochloride in the treatment of coma after surgery for cerebral hemorrhage and to explore its possible mechanism of action.Methods Seventy-two ...Objective To observe the efficacy of acupuncture combined with naloxone hydrochloride in the treatment of coma after surgery for cerebral hemorrhage and to explore its possible mechanism of action.Methods Seventy-two patients were divided into a control group and an observation group according to the random number table method,with 36 cases in each group.The control group was treated with intravenous naloxone hydrochloride,and the observation group received additional acupuncture treatment.After 1 month of treatment,the awakening rate,Glasgow coma scale(GCS)score,cerebral edema volume,mean velocity(Vm)of the middle cerebral artery,and cerebrospinal fluid Caspase-3,and macrophage migration inhibitory factor(MIF)levels were compared between the two groups.Results During the study,there were 2 cases of shedding in the control group and 34 remaining valid cases;1 case of shedding in the observation group and 35 remaining valid cases.After treatment,the awakening rate was higher in the observation group than in the control group(P<0.05);the GCS score increased in both groups compared with that before treatment(P<0.05),and was higher in the observation group than in the control group(P<0.05);the volume of cerebral edema decreased in both groups(P<0.05),and was smaller in the observation group than in the control group(P<0.05);the middle cerebral artery Vm increased in both groups(P<0.05),and was higher in the observation group than in the control group(P<0.05);the cerebrospinal fluid Caspase-3 and MIF levels decreased significantly in both groups(P<0.05)and were lower in the observation group than in the control group(P<0.05).Conclusion Acupuncture combined with naloxone hydrochloride for the treatment of coma after surgery for cerebral hemorrhage can promote patients’awakening,improve the degree of coma,reduce the volume of cerebral edema,and enhance cerebral blood flow velocity,producing a better effect than naloxone hydrochloride used alone;it may be related to its reduction of cerebrospinal fluid Caspase-3 and MIF levels.展开更多
文摘Objective To investigate the analgesia induced by receptin （REC）, a chemically modified cobratoxin （CTX, a long-chain postsynaptic α-neurotoxin from Thailand cobra venom）, and the effects of atropine and naloxone on antinociceptive activity of REC in rodent pain models. Methods REC was administered intraperitoneally （5 mg/kg, 7.07 mg/kg, or 10 mg/kg, i.p.） or intra-cerebral venticularly （62.5 μg/kg, i.c.v.）. The antinociceptive action was determined using the hotlate test, the acetic acid writhing test and tail flick assay in mice and rats. The involvement of cholinergic and the opioid peptidergic systems in REC-induced analgesia were examined by pretreatment of animals with atropine （Atr; 0.5 mg/kg, i.m. or 10 mg/kg, i.p.） or naloxone （Nal; 3 mg/kg, i.p.）. The effect of REC on motor activity was tested using the Animex test in mice. Results REC （5 mg/kg, 7.07 mg/kg or 10 mg/kg, i.p.） exhibited a dose-dependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. The significant analgesia of REC was seen 2 h to 3 h after its administration. In the rat-tail flick assay, the administration of REC at 62.5 μg/kg （1/160 of systemic dose; i.c.v.）produced marked analgesic effects. Atropine at 0.5 mg/kg （i.m.）, 10 mg/kg （i.p.） or naloxone at 3 mg/kg （i.p.） failed to block the analgesic effects of REC. REC at the highest effective dose of 10 mg/kg did not change the spontaneous mobility of mice. Conclusion These results demonstrate that REC has analgesic effect. This activity appears to be mediated through the peripheral nervous system though central nervous system may contribute to REC＇s analgesic effects. The central cholinergic system and opioid peptidergic system appear not to be involved in the antinociceptive action of REC.
文摘The pharmacokinetics and absolute bioavailability of the sublingual naloxone tablet were studied with HPLC-electrochemical detection. Eight male dogs received single 5 mg dose of naloxone intravenously, the plasma concentration-time curves could be fitted to two-compartment open model, with 12.0 min of t1/2( , 143.4 min of t1/2( and 7.92 mg(min/L of AUC. The same eight dogs received 5 mg dose of the sublingual naloxone tablet after an interval of a week. The main pharmacokinetic parameters were: t1/2ka = 11.0 min, t1/2( = 15.4 min, t1/2( = 164.1 min, Tmax = 27.7 min, Cmax = 34.2 ng / ml, and AUC = 6.79 mg(min / L, respectively. The plasma concentration-time curves were fitted to the first order absorption two-compartment open model also. The mean absolute bioavailability of the sublingual naloxone tablet was 86.8 ( 10.9%. No statistically significant differences were found with t1/2(, t1/2(, ( and ( between the two routes of administration. These results indicated that the course of disposition for naloxone in dogs was similar for the two routes of administration, and the absolute bioavailability of the sublingual naloxone tablet was high. Thus satisfactory clinical effects could be expected.
文摘I read with great interest the recent article by Chen et al in a recent issue of your esteemed journal.The article is highly thought provoking.One emerging therapeutic alternative for opioid induced constipation is the emergence of opioid/naloxone prolonged release combinations.For instance,naloxone when administered in a 1:2 ratio with oxycodone reverses the inhibitory effect of oxycodone on the gastrointestinal tract.The advantage of oxycodone/naloxone prolonged release(OXN) is that while its anti-nociceptive efficacy is equivalent to that of oxycodone prolonged release(OXC),it significantly decreases the "Bowel Function Index" thereby ameliorating symptoms of opioid induced constipation to a large extent.Schutter et al in a recent study have reported a decrease in the bowel function index from 38.2 to 15.1.Similarly,L wenstein et al in another recent study have reported that following a month of therapy,complete spontaneous bowel movements per week is increased from one in OXC therapy to three in OXN therapy.
文摘Naloxone is a well-known opioid antagonist indicated for the treatment of CNS （central nervous system） and respiratory depression induced by natural or synthetic opioid in adults and neonates whose mothers have received opioids. While it has been reported that an injection of 0.2 mg/mL of naloxone hydrochloride is physically and chemically stable, data on photostability on continuous i.v. infusion of 0.2 mg/mL of naloxone hydrochloride has not been reported. Therefore, a method was required for assessment of naloxone hydrochloride photostability. A high performance LC-MS （liquid chromatography/mass spectrometry） method was established to evaluate the photostability of naloxone hydrochloride. Injections of naloxone hydrochloride in 0.9% sodium chloride were exposed to artificial light and stored at room temperature （22 ~C） and 37 ~C. Naloxone losses up to 9.79% of its initial concentration when exposed to light at room temperature for 192 h, but the degradation increased up to 14.91% as the storage temperature increase. The disappearance of naloxone hydrochloride was correlated with the appearance of nor-oxymorphonedegradant. Naloxone hydrochloride is photosensitive and degradation increased at highly temperature and light intensity. Therefore, naloxone i.v. infusion solutions should either be protected from light and/or be frequently replaced when being administered to patients.
文摘Objective To observe the efficacy of acupuncture combined with naloxone hydrochloride in the treatment of coma after surgery for cerebral hemorrhage and to explore its possible mechanism of action.Methods Seventy-two patients were divided into a control group and an observation group according to the random number table method,with 36 cases in each group.The control group was treated with intravenous naloxone hydrochloride,and the observation group received additional acupuncture treatment.After 1 month of treatment,the awakening rate,Glasgow coma scale(GCS)score,cerebral edema volume,mean velocity(Vm)of the middle cerebral artery,and cerebrospinal fluid Caspase-3,and macrophage migration inhibitory factor(MIF)levels were compared between the two groups.Results During the study,there were 2 cases of shedding in the control group and 34 remaining valid cases;1 case of shedding in the observation group and 35 remaining valid cases.After treatment,the awakening rate was higher in the observation group than in the control group(P<0.05);the GCS score increased in both groups compared with that before treatment(P<0.05),and was higher in the observation group than in the control group(P<0.05);the volume of cerebral edema decreased in both groups(P<0.05),and was smaller in the observation group than in the control group(P<0.05);the middle cerebral artery Vm increased in both groups(P<0.05),and was higher in the observation group than in the control group(P<0.05);the cerebrospinal fluid Caspase-3 and MIF levels decreased significantly in both groups(P<0.05)and were lower in the observation group than in the control group(P<0.05).Conclusion Acupuncture combined with naloxone hydrochloride for the treatment of coma after surgery for cerebral hemorrhage can promote patients’awakening,improve the degree of coma,reduce the volume of cerebral edema,and enhance cerebral blood flow velocity,producing a better effect than naloxone hydrochloride used alone;it may be related to its reduction of cerebrospinal fluid Caspase-3 and MIF levels.
