Topic
Leconotide
About: Leconotide is a research topic. Over the lifetime, 3 publications have been published within this topic receiving 90 citations.
Papers
1 Jan 2016
TL;DR: Leconotide caused a significant increase in reversal by morphine of the bone cancer- induced hyperalgesia without increasing the side effect profile of either drug.
Abstract: Objective. Leconotide (CVID, AM336, CNSB004) is an omega conopeptide similar to ziconotide, which blocks voltage sensitive calcium channels. However, unlike ziconotide, which must be administered intrathecally, leconotide can be given intravenously because it is less toxic. This study investigated the antihyperalgesic potency of leconotide given intra- venously alone and in combinations with morphine- administered intraperitoneally, in a rat model of bone cancer pain. Design. Syngeneic rat prostate cancer cells AT3B-1 were injected into one tibia of male Wistar rats. The tumor expanded within the bone causing hyperalge- sia to heat applied to the ipsilateral hind paw. Mea- surements were made of the maximum dose (MD) of morphine and leconotide given alone and in combi- nations that caused no effect in an open-field activ- ity monitor, rotarod, and blood pressure and heart rate measurements. Paw withdrawal thresholds from noxious heat were measured. Dose response curves for morphine (0.312-5.0 mg/kg intraperito- neal) and leconotide (0.002-200 mg/kg intravenous) given alone were plotted and responses compared with those caused by morphine and leconotide in combinations. Results. Leconotide caused minimal antihyperalge- sic effects when administered alone. Morphine given alone intraperitoneally caused dose-related antihyperalgesic effects (ED50 = 2.40 1.24 mg/kg), which were increased by coadministration of leconotide 20 mg/kg (morphine ED50 = 0.16 1.30 mg/kg); 0.2 mg/kg (morphine ED50 = 0.39 1.27 mg/kg); and 0.02 mg/kg (morphine ED50 = 1.24 1.30 mg/kg). Conclusions. Leconotide caused a significant increase in reversal by morphine of the bone cancer- induced hyperalgesia without increasing the side effect profile of either drug. Clinical Implication. Translation into clinical prac- tice of the method of analgesia described here will improve the quantity and quality of analgesia in patients with bone metastases. The use of an ordi- nary parenteral route for administration of the calcium channel blocker (leconotide) at low dose opens up the technique to large numbers of patients who could not have an intrathecal catheter for drug administration. Furthermore, the potentiating syner- gistic effect with morphine on hyperalgesia without increased side effects will lead to greater analgesia with improved quality of life.
TL;DR: In this paper, the authors investigated the antihyperalgesic potency of leconotide given intravenously alone and in combinations with morphine-administered intraperitoneally, in a rat model of bone cancer pain.
Abstract: Objective. Leconotide (CVID, AM336, CNSB004) is an omega conopeptide similar to ziconotide, which blocks voltage sensitive calcium channels. However, unlike ziconotide, which must be administered intrathecally, leconotide can be given intravenously because it is less toxic. This study investigated the antihyperalgesic potency of leconotide given intravenously alone and in combinations with morphine-administered intraperitoneally, in a rat model of bone cancer pain. Design. Syngeneic rat prostate cancer cells AT3B-1 were injected into one tibia of male Wistar rats. The tumor expanded within the bone causing hyperalgesia to heat applied to the ipsilateral hind paw. Measurements were made of the maximum dose (MD) of morphine and leconotide given alone and in combinations that caused no effect in an open-field activity monitor, rotarod, and blood pressure and heart rate measurements. Paw withdrawal thresholds from noxious heat were measured. Dose response curves for morphine (0.312–5.0 mg/kg intraperitoneal) and leconotide (0.002–200 µg/kg intravenous) given alone were plotted and responses compared with those caused by morphine and leconotide in combinations. Results. Leconotide caused minimal antihyperalgesic effects when administered alone. Morphine given alone intraperitoneally caused dose-related antihyperalgesic effects (ED50 = 2.40 ± 1.24 mg/kg), which were increased by coadministration of leconotide 20 µg/kg (morphine ED50 = 0.16 ± 1.30 mg/kg); 0.2 µg/kg (morphine ED50 = 0.39 ± 1.27 mg/kg); and 0.02 µg/kg (morphine ED50 = 1.24 ± 1.30 mg/kg). Conclusions. Leconotide caused a significant increase in reversal by morphine of the bone cancer-induced hyperalgesia without increasing the side effect profile of either drug. Clinical Implication. Translation into clinical practice of the method of analgesia described here will improve the quantity and quality of analgesia in patients with bone metastases. The use of an ordinary parenteral route for administration of the calcium channel blocker (leconotide) at low dose opens up the technique to large numbers of patients who could not have an intrathecal catheter for drug administration. Furthermore, the potentiating synergistic effect with morphine on hyperalgesia without increased side effects will lead to greater analgesia with improved quality of life.
TL;DR: Leconotide could have wider clinical applications than ziconotide and powerful antihyperalgesia without side effects can be achieved by intravenous administration of leconotide thus avoiding the need for an intrathecal injection.
Abstract: Objective. Leconotide is an ω-conotoxin that blocks neuronal voltage sensitive calcium channels. This study compared the antihyperalgesic potencies of leconotide and ziconotide given intravenously alone and in combinations with a potassium channel modulator flupirtine, given intraperitoneally, in a rat model of diabetic neuropathic pain.
Design. Rats were given streptozotocin (150 mg/kg ip) to induce diabetic neuropathy and hyperalgesia. Experiments were performed on diabetic rats with ≥30% hyperalgesia to noxious heat. Rats were given each conopeptide alone and with flupirtine. Open field activity monitoring and non-invasive blood pressure measurements were used to define the maximum doses and combinations that caused no side effects. Doses in a range up to maximum no side effect doses were tested for antihyperalgesic effects in rats with hyperalgesia.
Results. The maximum no side effect dose of leconotide (2 mg/kg intravenously) caused 51.7% reversal of hyperalgesia compared with 0.4% for the highest no side effect dose of ziconotide (0.02 mg/kg; P < 0.001, one-way anova). Leconotide caused dose-related antihyperalgesic effects that were potentiated by coadministration with flupirtine at doses that were ineffective when given alone. Leconotide (0.02 mg/kg) and flupirtine (5 mg/kg) caused 25.3 ± 7.6 and −6 ± 9.5% reversal of hyperalgesia, respectively when given alone but in combination they caused 84.1 ± 7.2% reversal of hyperalgesia (P < 0.01; one-way anova). No such interaction occurred with ziconotide.
Conclusion. Leconotide could have wider clinical applications than ziconotide. Unlike ziconotide, powerful antihyperalgesia without side effects can be achieved by intravenous administration of leconotide thus avoiding the need for an intrathecal injection.
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2016 | 1 |
| 2011 | 1 |
| 2010 | 1 |