am336 and Pain

am336 has been researched along with Pain* in 4 studies

Other Studies

4 other study(ies) available for am336 and Pain

ArticleYear
Novel ω-conotoxins from C. catus reverse signs of mouse inflammatory pain after systemic administration.
    Molecular pain, 2013, Oct-20, Volume: 9

    Antagonists of N-type voltage-gated calcium channels (VGCC), Ca(v)2.2, can manage severe chronic pain with intrathecal use and may be effective systemically. A series of novel ω-conotoxins that selectively inhibit N-type VGCCs was isolated from Conus catus. In the present study, the potency and reversibility of ω-conotoxins CVID, CVIE and CVIF to inhibit N-type calcium currents were investigated in mouse isolated dorsal root ganglion (DRG) neurons. The systemic potency of each ω-conotoxin to reverse signs of mouse chronic inflammatory pain was also compared.. In DRG neurons, the rank order of potency to inhibit N-type calcium currents was CVIE > CVIF > CVID. After subcutaneous administration, CVID and CVIE, but not CVIF, partially reversed impaired weight bearing in mice injected with Freund's complete adjuvant (CFA) three days prior to testing. No side-effects associated with systemic administration of ω-conotoxins were observed.. The present study indicates a potential for CVID and CVIE to be developed as systemically active analgesics with no accompanying neurological side-effects.

    Topics: Analgesics; Animals; Calcium Channel Blockers; Calcium Channels, N-Type; Male; Mice; Mice, Inbred C57BL; omega-Conotoxins; Pain; Patch-Clamp Techniques

2013
Intravenous injection of leconotide, an omega conotoxin: synergistic antihyperalgesic effects with morphine in a rat model of bone cancer pain.
    Pain medicine (Malden, Mass.), 2011, Volume: 12, Issue:6

    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.. 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.. Leconotide 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).. Leconotide caused a significant increase in reversal by morphine of the bone cancer-induced hyperalgesia without increasing the side effect profile of either drug.. 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.

    Topics: Analgesics; Animals; Behavior, Animal; Bone Neoplasms; Dose-Response Relationship, Drug; Drug Synergism; Hyperalgesia; Injections, Intravenous; Male; Morphine; Neoplasm Transplantation; Neuropsychological Tests; omega-Conotoxins; Pain; Pain Measurement; Rats; Rats, Wistar; Tibia; Tumor Cells, Cultured

2011
Inflammation reduces the contribution of N-type calcium channels to primary afferent synaptic transmission onto NK1 receptor-positive lamina I neurons in the rat dorsal horn.
    The Journal of physiology, 2007, May-01, Volume: 580, Issue:Pt.3

    N-type calcium channels contribute to the release of glutamate from primary afferent terminals synapsing onto nocisponsive neurons in the dorsal horn of the spinal cord, but little is known of functional adaptations to these channels in persistent pain states. Subtype-selective conotoxins and other drugs were used to determine the role of different calcium channel types in a rat model of inflammatory pain. Electrically evoked primary afferent synapses onto lumber dorsal horn neurons were examined three days after induction of inflammation with intraplantar complete Freund's adjuvant. The maximal inhibitory effect of the N-type calcium channel blockers, omega-conotoxins CVID and MVIIA, were attenuated in NK1 receptor-positive lamina I neurons after inflammation, but the potency of CVID was unchanged. This was associated with reduced inhibition of the frequency of asynchronous-evoked synaptic events by CVID studied in the presence of extracellular strontium, suggesting reduced N-type channel contribution to primary afferent synapses after inflammation. After application of CVID, the relative contributions of P/Q and L channels to primary afferent transmission and the residual current were unchanged by inflammation, suggesting the adaptation was specific to N-type channels. Blocking T-type channels did not affect synaptic amplitude under control or inflamed conditions. Reduction of N-type channel contribution to primary afferent transmission was selective for NK1 receptor-positive neurons identified by post hoc immunohistochemistry and did not occur at synapses in laminae II(o) or II(i), or inhibitory synapses. These results suggest that inflammation selectively downregulates N-type channels in the terminals of primary afferents synapsing onto (presumed) nociceptive lamina I NK1 receptor-positive neurons.

    Topics: Afferent Pathways; Animals; Calcium Channels, N-Type; Chronic Disease; Down-Regulation; Electric Stimulation; Evoked Potentials; Female; Freund's Adjuvant; Hindlimb; Inflammation; Male; Nociceptors; omega-Conotoxins; Pain; Posterior Horn Cells; Rats; Rats, Sprague-Dawley; Receptors, Neurokinin-1; Spinal Cord; Synapses; Synaptic Transmission; Venoms

2007
Actions of intrathecal omega-conotoxins CVID, GVIA, MVIIA, and morphine in acute and neuropathic pain in the rat.
    European journal of pharmacology, 2002, Sep-20, Volume: 451, Issue:3

    Agents which decrease conductance of N-type voltage-gated Ca(2+) channels have been shown to attenuate measures of neuropathic pain in animal models and to provide symptom relief in humans. The omega-conotoxins have demonstrated efficacy but have a low therapeutic index. We have investigated the effects of a new omega-conotoxin, CVID (AM-336), and compared them with omega-conotoxin GVIA (SNX-124), omega-conotoxin MVIIA (SNX-111) and morphine in a spinal nerve ligation model of neuropathic pain in the rat. The ED(50) (and 95% CI) for attenuation of tactile allodynia by intrathecal administration for omega-conotoxin CVID, GVIA, MVIIA and morphine was 0.36 (0.27-0.48), 0.12 (0.06-0.24), 0.32 (0.23-0.45) and 4.4 (2.9-6.5) microg/kg, respectively. Only morphine significantly prolonged acute tail flick responses (ED(50) 2.3 (1.1-4.9) microg/kg). Of the omega-conotoxins, omega-conotoxin CVID showed the highest ratio of efficacy to behavioural toxicity. These observations show that intrathecal omega-conotoxins are effective in attenuating tactile allodynia in the rat without significantly affecting acute nociceptive responses. Omega-conotoxin CVID had similar potency to omega-conotoxin MVIIA but showed less toxicity in the therapeutic range.

    Topics: Analysis of Variance; Animals; Calcium Channel Blockers; Dose-Response Relationship, Drug; Injections, Spinal; Male; Morphine; omega-Conotoxin GVIA; omega-Conotoxins; Pain; Rats; Rats, Sprague-Dawley; Venoms

2002