Use of Intrathecal SNX-111, a Novel, N-Type, Voltage-Sensitive, Calcium Channel Blocker, in the Management of Intractable Brachial Plexus Avulsion Pain

Brose, William G.; Gutlove, David P.; Luther, Robert R.; Bowersox, S. Scott; McGuire, Dawn

doi:10.1097/00002508-199709000-00012

Cited by 128 publications

(74 citation statements)

References 10 publications

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“…A dose-dependent analgesic effect of continuous it infusion of SNX-111 was demonstrated in one case of intractable deafferentation and phantom limb pain secondary to brachial plexus avulsion and subsequent amputation (58). Thirty patients undergoing elective abdominal hysterectomy, radical prostatectomy or total hip replacement were treated with an it infusion of SNX-111 (ziconotide, 0.7 to 7.0 µg/h), which was started before the surgical incision and continued for 48 to 72 h postoperatively.…”

Section: Clinical Studiesmentioning

confidence: 97%

Involvement of calcium in pain and antinociception

2001

Braz J Med Biol Res

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Calcium ions are widely recognized to play a fundamental role in the regulation of several biological processes. Transient changes in cytoplasmic calcium ion concentration represent a key step for neurotransmitter release and the modulation of cell membrane excitability. Evidence has accumulated for the involvement of calcium ions also in nociception and antinociception, including the analgesic effects produced by opioids. The combination of opioids with drugs able to interfere with calcium ion functions in neurons has been pointed out as a useful alternative for safer clinical pain management. Alternatively, drugs that reduce the flux of calcium ions into neurons have been indicated as analgesic alternatives to opioids. This article reviews the manners by which calcium ions penetrate cell membranes and the changes in these mechanisms caused by opioids and calcium antagonists regarding nociceptive and antinociceptive events.

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Section: Clinical Studiesmentioning

confidence: 97%

Involvement of calcium in pain and antinociception

2001

Braz J Med Biol Res

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“…However, ziconotide must be intrathecally injected to be efficacious and can induce undesirable side-effects. [3][4][5][6][7][8][9][10]21,60,61) Future directions include development of a novel class of N-type VDCC blockers with improved oral efficacy and better safety profile. Similar to ziconotide, cilnidipine is considered to be efficacious in tissue-and nerve-injured animal models with little effect on acute physiological pain, although systematic estimation of cilnidipine for antinociception remains to be performed.…”

Section: 237-41)mentioning

confidence: 99%

“…1,2) Ziconotide (also known as SNX-111), a synthetic form of w-conotoxin MVIIA and an N-type VDCC blocker, exerts potent antinociceptive effects when injected intrathecally in animal models and clinical situations. [3][4][5][6][7][8][9][10] Furthermore, N-type VDCC dysfunction resulting from N-type VDCC knockout in mice leads to higher nociceptive thresholds than in wild-type mice. [11][12][13][14] N-type VDCCs are thus an important drug target for treatment of chronic pain.…”

mentioning

confidence: 99%

Suppression of Formalin-Induced Nociception by Cilnidipine, a Voltage-Dependent Calcium Channel Blocker

Koganei

Shoji

Iwata

2009

Biological & Pharmaceutical Bulletin

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Cilnidipine is a 1,4-dihydropyridine-derived voltage-dependent calcium channel (VDCC) blocker and suppresses N-type VDCC currents in addition to L-type VDCC currents. An earlier investigation has suggested that intrathecally injected cilnidipine produces antinociception by blocking N-type VDCCs in mice. The present study using the rat formalin model examined antinociceptive effects of intrathecally and orally administered cilnidipine to elucidate a putative site of antinociception of cilnidipine, assess the efficacy of oral cilnidipine for pain relief, and clarify the mechanism(s) responsible for the antinociceptive effect of oral cilnidipine. Cilnidipine (whether intrathecal or oral) suppressed nociception in phases 1 and 2 of the formalin model. In addition, the potency of oral cilnidipine to suppress formalin-induced nociception in phase 2 was greater than that of oral gabapentin, a clinically available drug for treatment of neuropathic pain. Cilnidipine elicited antinociceptive effects without neurological side-effects including serpentine-like tail movement, whole body shaking, and allodynia. Such side-effects can be induced by higher doses of intrathecal ziconotide, a clinically available N-type VDCC blocker. In contrast, orally administered nifedipine, an L-type VDCC blocker, had no effect on either phase of formalin-induced nociception. These results suggest that cilnidipine acts on the spinal cord to produce antinociception and is efficacious for pain relief after oral administration with better safety profile than that of ziconotide. Furthermore, the failure of orally administered nifedipine to affect formalin-induced nociception raises the possibility that oral cilnidipine produces antinociception through, at least in part, spinal N-type VDCC blockade.

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“…Ziconotide was the first selective N-type calcium channel blocker to be tested in clinical trials and has recently been approved for the treatment of severe chronic pain associated with cancer, AIDS and neuropathies, under the trade name Prialt s (Atanassoff et al, 2000;Brose et al, 1997;McGivern, 2007;Miljanich, 2004;Staats et al, 2004). Although Prialt does not induce tolerance and shows efficacy in patients refractory to opioid therapies, it is not without limitations.…”

Section: Voltage-gated Ion Channels: Novel Approaches To Modulation Omentioning

confidence: 99%

Drugability of Extracellular Targets: Discovery of Small Molecule Drugs Targeting Allosteric, Functional, and Subunit-Selective Sites on GPCRs and Ion Channels

Grigoriadis

Hoare

Lechner

et al. 2008

Neuropsychopharmacol

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Beginning with the discovery of the structure of deoxyribose nucleic acid in 1953, by James Watson and Francis Crick, the sequencing of the entire human genome some 50 years later, has begun to quantify the classes and types of proteins that may have relevance to human disease with the promise of rapidly identifying compounds that can modulate these proteins so as to have a beneficial and therapeutic outcome. This so called 'drugable space' involves a variety of membrane-bound proteins including the superfamily of G-protein-coupled receptors (GPCRs), ion channels, and transporters among others. The recent number of novel therapeutics targeting membrane-bound extracellular proteins that have reached the market in the past 20 years however pales in magnitude when compared, during the same timeframe, to the advancements made in the technologies available to aid in the discovery of these novel therapeutics. This review will consider select examples of extracellular drugable targets and focus on the GPCRs and ion channels highlighting the corticotropin releasing factor (CRF) type 1 and g-aminobutyric acid receptors, and the Ca V 2.2 voltage-gated ion channel. These examples will elaborate current technological advancements in drug discovery and provide a prospective framework for future drug development.

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Use of Intrathecal SNX-111, a Novel, N-Type, Voltage-Sensitive, Calcium Channel Blocker, in the Management of Intractable Brachial Plexus Avulsion Pain

Cited by 128 publications

References 10 publications

Involvement of calcium in pain and antinociception

Involvement of calcium in pain and antinociception

Suppression of Formalin-Induced Nociception by Cilnidipine, a Voltage-Dependent Calcium Channel Blocker

Drugability of Extracellular Targets: Discovery of Small Molecule Drugs Targeting Allosteric, Functional, and Subunit-Selective Sites on GPCRs and Ion Channels

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