omegaconotoxins

Omega-conotoxins are a subset of conotoxins produced by predatory marine cone snails (genus Conus). They are small, cysteine-rich peptide toxins that act on presynaptic voltage-gated calcium channels, with high affinity for the N-type Cav2.2 channel. By blocking these channels, omega-conotoxins reduce calcium entry into nerve terminals and suppress neurotransmitter release, producing potent analgesia in pain pathways.

Chemistry and structure: omega-conotoxins are typically 20–30 amino acids long and stabilized by multiple disulfide bonds, forming compact three-dimensional folds. They often undergo post-translational modifications common to conotoxins, contributing to their stability and activity.

Mechanism and pharmacology: the primary target is Cav2.2 channels on presynaptic neurons. Inhibition of calcium influx during action potentials decreases release of excitatory transmitters such as glutamate, calcitonin gene-related peptide, and substance P, effectively dampening nociceptive signaling.

Medical relevance: several omega-conotoxins have been studied as analgesics. Ziconotide, the synthetic form of omega-conotoxin MVIIA, is approved for the treatment of severe chronic pain and is administered intrathecally. It is a non-opioid analgesic, but requires careful patient selection and monitoring due to side effects such as dizziness, confusion, and psychiatric symptoms.

Discovery and research: omega-conotoxins were identified from Conus venoms in the latter part of the 20th century, with MVIIA and GVIA among the best characterized examples. Beyond clinical use, these toxins serve as important tools in neurophysiology for understanding presynaptic calcium signaling.

Toxicology and safety: in venom, they contribute to prey immobilization; in therapeutic contexts, dosing must be precise to balance analgesia against adverse effects.