ziconotide and Tremor

ziconotide has been researched along with Tremor* in 2 studies

Other Studies

2 other study(ies) available for ziconotide and Tremor

ArticleYear
TAT-Modified ω-Conotoxin MVIIA for Crossing the Blood-Brain Barrier.
    Marine drugs, 2019, May-12, Volume: 17, Issue:5

    As the first in a new class of non-opioid drugs, ω-Conotoxin MVIIA was approved for the management of severe chronic pains in patients who are unresponsive to opioid therapy. Unfortunately, clinical application of MVIIA is severely limited due to its poor ability to penetrate the blood-brain barrier (BBB), reaching the central nervous system (CNS). In the present study, we have attempted to increase MVIIA's ability to cross the BBB via a fusion protein strategy. Our results showed that when the TAT-transducing domain was fused to the MVIIA C-terminal with a linker of varied numbers of glycine, the MVIIA-TAT fusion peptide exhibited remarkable ability to cross the bio-membranes. Most importantly, both intravenous and intranasal administrations of MVIIA-TAT in vivo showed therapeutic efficacy of analgesia. Compared to the analgesic effects of intracerebral administration of the nascent MVIIA, these systemic administrations of MVIIA-TAT require higher doses, but have much prolonged effects. Taken together, our results showed that TAT conjugation of MVIIA not only enables its peripheral administration, but also maintains its analgesic efficiency with a prolonged effective time window. Intranasal administration also rendered the MVIIA-TAT advantages of easy applications with potentially reduced side effects. Our results may present an alternative strategy to improve the CNS accessibility for neural active peptides.

    Topics: Analgesics; Animals; Blood-Brain Barrier; Calcium Channel Blockers; Female; Male; Mice; omega-Conotoxins; Pain; Pain Measurement; Peptides; Recombinant Fusion Proteins; RNA-Binding Protein FUS; tat Gene Products, Human Immunodeficiency Virus; Tremor

2019
Molecular basis of toxicity of N-type calcium channel inhibitor MVIIA.
    Neuropharmacology, 2016, Volume: 101

    MVIIA (ziconotide) is a specific inhibitor of N-type calcium channel, Cav2.2. It is derived from Cone snail and currently used for the treatment of severe chronic pains in patients unresponsive to opioid therapy. However, MVIIA produces severe side-effects, including dizziness, nystagmus, somnolence, abnormal gait, and ataxia, that limit its wider application. We previously identified a novel inhibitor of Cav2.2, ω-conopeptide SO-3, which possesses similar structure and analgesic activity to MVIIA's. To investigate the key residues for MVIIA toxicity, MVIIA/SO-3 hybrids and MVIIA variants carrying mutations in its loop 2 were synthesized. The substitution of MVIIA's loop 1 with the loop 1 of SO-3 resulted in significantly reduced Cav2.2 binding activity in vitro; the replacement of MVIIA loop 2 by the loop 2 of SO-3 not only enhanced the peptide/Cav2.2 binding but also decreased its toxicity on goldfish, attenuated mouse tremor symptom, spontaneous locomotor activity, and coordinated locomotion function. Further mutation analysis and molecular calculation revealed that the toxicity of MVIIA mainly arose from Met(12) in the loop 2, and this residue inserts into a hydrophobic hole (Ile(300), Phe(302) and Leu(305)) located between repeats II and III of Cav2.2. The combinative mutations of the loop 2 of MVIIA or other ω-conopeptides may be used for future development of more effective Cav2.2 inhibitors with lower side effects.

    Topics: Animals; Calcium Channel Blockers; Calcium Channels, N-Type; Goldfish; HEK293 Cells; Humans; Locomotion; Male; Membrane Potentials; Mice; Mice, Inbred Strains; Motor Disorders; Mutation; Neuralgia; omega-Conotoxins; Peptides; Protein Conformation; Protein Structure, Secondary; Rats; Rats, Sprague-Dawley; Reaction Time; Sequence Homology, Amino Acid; Tremor

2016