Conantokins are a small family of helical peptides that are derived from the venom of predatory marine snails of the genus Conus.
[2] The subtypes of conantokins exhibit a surprising variability of selectivity across the NMDAR subunits, and are therefore uniquely useful in developing subunit-specific pharmacological probes.
[8] Conantokin are in general named after the specific epithet of the Conus species it is found in, using single-letter abbreviations if possible.
[11] Con-G shows potential as a neuroprotective agent in ischemic and excitotoxic brain injury, neuronal apoptosis, pain, epilepsy, and as a research tool in drug addiction and Alzheimer's disease.
Con-G reduces the strength of excitotoxic intracellular Ca2+ actions and blocks different neuronal injuries in vitro.
[5] Con-L blocks NMDA-evoked currents in a powerful way, which is only slowly reversible upon washout, similar to Con-R and Con-G.[5] Each peptide in this group is derived from the same species, Conus parius.
[1] Con-Rl-A (P0DKY9), derived from the venom of Conus rolani, is unique among the conantokins in having two distinct conformational states between which it equilibrates.
Like Con-P and Con-E, its helical structure (estimated at 50%) does not depend on the presence or absence of calcium.
The inhibition of NMDAR-mediated spontaneous EPSCs (sEPSCs) and NMDA-gated currents in cortical neurons might be a result of actions on both diheteromeric (NR1/NR2B) and triheteromeric (NR1/NR2A/NR2B) NMDAR.
[11][17] It can attenuate both the amplitude and the decay time constant of NMDA-mediated EPSCs[18] and significantly and reversibly affect other different properties of NMDAR-mediated sEPSCs in cultured neurons.
[3] Intrathecal administration of doses greater than 300 pmol produced motor impairment in mice.