OBJECTIVELeconotide (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.DESIGNSyngeneic 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.RESULTSLeconotide caused minimal antihyperalgesic effects when administered alone. Morphine given alone intraperitoneally caused dose-related antihyperalgesic effects (ED(50) = 2.40 ± 1.24 mg/kg), which were increased by coadministration of leconotide 20 µg/kg (morphine ED(50) = 0.16 ± 1.30 mg/kg); 0.2 µg/kg (morphine ED(50) = 0.39 ± 1.27 mg/kg); and 0.02 µg/kg (morphine ED(50) = 1.24 ± 1.30 mg/kg).CONCLUSIONSLeconotide caused a significant increase in reversal by morphine of the bone cancer-induced hyperalgesia without increasing the side effect profile of either drug.CLINICAL IMPLICATIONTranslation 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.

2010-02-01·Pain Medicine3区 · 医学

CNSB004 (Leconotide) Causes Antihyperalgesia Without Side Effects When Given Intravenously: A Comparison with Ziconotide in a Rat Model of Diabetic Neuropathic Pain

3区 · 医学

Article

作者: Ian Cooke ; Colin Stanley Goodchild ; Anton Kolosov

OBJECTIVELeconotide is an omega-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.DESIGNRats were given streptozotocin (150 mg/kg ip) to induce diabetic neuropathy and hyperalgesia. Experiments were performed on diabetic rats with >or=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.RESULTSThe 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.CONCLUSIONLeconotide 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.

2008-04-01·Neuromodulation: Technology at the Neural Interface2区 · 医学

Future Directions for Intrathecal Pain Management: A Review and Update From the Interdisciplinary Polyanalgesic Consensus Conference 2007

2区 · 医学

Article

作者: Mark Wallace ; Leong Liem ; Gladstone McDowell ; Elliot S. Krames ; Michael Stanton-Hicks ; Allen Burton ; K. Dean Willis ; Samuel Hassenbusch ; Mark Huntoon ; Michael Saulino ; Michael Erdek ; James Rathmell ; Peter Staats ; Todd Sitzman ; Kenneth Follett ; Nagy Mekhail ; James Eisenach ; William Witt ; Sunil Panchal ; Joshua Prager ; Phillip Kim ; Robert Levy ; Michael Cousins ; David Caraway ; Ann Ver Donck ; Timothy Deer ; Eric Buchser ; Stuart Dupen ; Eric Grigsby ; Lisa Stearns ; Richard Rauck

Background. Expert panels of physicians and nonphysicians, all expert in intrathecal (IT) therapies, convened in the years 2000 and 2003 to make recommendations for the rational use of IT analgesics, based on the preclinical and clinical literature known up to those times, presentations of the expert panels, discussions on current practice and standards, and the result of surveys of physicians using IT agents. An expert panel of physicians and nonphysicians has convened in 2007 to update information known regarding IT therapies and to update information on new and novel opioid and nonopioid analgesic compounds that might show promise for IT use. Methods. A review of preclinical and clinical published relevant studies from 2000 to 2006 was undertaken and disseminated to a convened expert panel of physicians and nonphysicians to discuss new and novel analgesic agents for IT use. Results. The panelists identified several agents that were worthy of future studies for the clinical and rational use of IT agents that are presented in this article. Conclusions. A list of nonopioid IT analgesics, including gabapentin, adenosine, octreotide, the χ-conopeptide, Xen2174, the conopeptide, neurotensis 1 agonist, CGX-1160, the ω-conotoxin, AM-336, and physostigmine, were identified as worthy of future research by the panelists.

100 项与 Leconotide 相关的药物交易

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