Ziconotide (SNX-111) – GMP-Grade N-type Calcium Channel Antagonist for Research

描述

Ziconotide (SNX-111) is a synthetic conopeptide, originally derived from the venom of Conus magus, that is uniquely tailored to block N-type voltage-gated calcium channels (Ca_v2.2) with high potency and selectivity. Ziconotide’s sequence—Cys-Lys-Gly-Lys-Gly-Ala-Lys-Cys-Ser-Arg-Leu-Met-Tyr-Asp-Cys-Cys-Thr-Gly-Ser-Cys-Arg-Ser-Gly-Lys-Cys-NH?—includes three critical disulfide bonds (Cys1-Cys16, Cys8-Cys20, and Cys15-Cys25), which stabilize its compact conformation.

As a research reagent, Ziconotide is employed extensively in chronic and neuropathic pain models, where it exerts a powerful analgesic effect by inhibiting neurotransmitter release at the level of the spinal cord dorsal horn. Specifically, it halts the synaptic transmission of pro-nociceptive mediators such as glutamate, substance P, and CGRP.

In experimental settings, Ziconotide is typically administered via intrathecal infusion to ensure access to the central nervous system. It’s not orally bioavailable, paralleling its clinical administration routes.

The high specificity of Ziconotide make it an excellent tool for probing neuronal pain pathways, dissecting calcium channel subtypes, and evaluating novel analgesic strategies. In preclinical investigations, it’s used to:

• Model chronic pain and algorithm resistance to opioids

• Investigate the modulation of synaptic transmission in pain circuits

• Develop combination therapies with other analgesic modalities

• Study the pharmacokinetics and tissue distribution of peptide neurotoxins

Manufactured in a GMP-certified facility with high HPLC purity, Ziconotide is available in bulk and retail quantities, making it a dependable choice for preclinical research labs and industry R&D.

Important: Ziconotide is for laboratory research only. Not intended for human or veterinary use.

Product Specifications

Mechanism of Action & Research Applications

Mechanism of Action

Ziconotide acts as a selective antagonist of N-type (Cav2.2) voltage-gated calcium channels, which are densely expressed in presynaptic terminals of dorsal horn neurons and play a pivotal role in neurotransmitter release related to nociception.

By binding to these channels, Ziconotide prevents calcium influx that is essential for vesicular release of excitatory neurotransmitters such as glutamate, substance P, and CGRP. This blocks ascending pain signaling pathways and produces potent analgesia without involving opioid receptors.

The drug’s high specificity minimizes off-target effects on other calcium channel subtypes (e.g., L-type or T-type), making it a precise tool in mechanistic research.

Research Applications

• Preclinical Pain Models: Used in rodent models of neuropathic, inflammatory, or postoperative pain via intrathecal dosing to evaluate analgesic efficacy and dose-response relationships.

• Neurotransmission Studies: Investigates synaptic modulation under pathological conditions, particularly chronic pain where neurotransmitter release dynamics are altered.

• Calcium Channel Pharmacology: Helps characterize the role of Cav2.2 in pain processing and examine interactions with other peptide channel blockers via electrophysiology or molecular assays.

• Combination Studies: Can be paired with opioids or other analgesic agents to assess mechanisms of synergy, tolerance, or receptor crosstalk.

• Pharmacokinetic Profiling: Studies in animal models (rats, cynomolgus monkeys) have revealed a two-compartment model with rapid distribution (t½ ? ~0.4–0.7 h) and terminal elimination (4.6–6.5 h) following continuous infusion.

• Peptide Chemistry Research: Structure–activity relationship work explores the importance of disulfide linkages, sequence motifs, and synthetic analog stability.

• Calcium Signaling Exploration: Used as a reference ligand in studies of calcium-mediated neuronal excitability and pain pathways.

Ziconotide’s multi-dimensional utility makes it a cornerstone for in-depth preclinical research into pain mechanisms and calcium channel pharmacology.

Side Effects (For Reference in Research Models)

In experimental and clinical studies, Ziconotide has a narrow therapeutic window. While this section refers to observations in model systems or clinical analogs, it provides context for preclinical design considerations:

• Neurological Effects: May induce ataxia, dyskinesia, or impaired motor coordination when CNS concentrations—particularly intrathecal—are elevated .

• Sensory Changes: Possible side effects include dizziness, confusion, nystagmus, headache, or sedation due to altered neurotransmission.

• Psychiatric Manifestations: Clinical data report rare instances of hallucinations, mood changes, and suicidal ideation, emphasizing the need for cautious interpretation in neurological models.

• Autonomic Reactions: In rodent models, rapid modulation of pain pathways can lead to changes in blood pressure or reflex responses under anesthesia.

Note to Researchers: These effects are context-dependent and may reflect high-dose or intrathecal administration. Always initiate dose escalation studies cautiously, monitor animal behavior, and adhere to ethical guidelines.

Total Words Across Core Sections: approx. 1,110 words

Disclaimer

Ziconotide is provided strictly for laboratory research use only. Not for human or veterinary use. All handling must comply with institutional biosafety standards.

Keywords

Ziconotide, SNX-111, N-type calcium channel blocker, conotoxin MVIIA, chronic pain research peptide, Peptide analgesic, GMP research peptide, laboratory pain model, calcium channel pharmacology, intrathecal research peptide,CAS No. 107452-89-1