Conantokins are a small family of helical peptides that are derived from the venom of predatory marine snails of the genus Conus. Conantokins act as potent and specific antagonists of the N-methyl-D-aspartate receptor (NMDAR). They are the only naturally-derived peptides to do so. 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. Chemically, conantokins are unique in that they possess a number (generally 4 or 5) of gamma-carboxyglutamyl (Gla) residues, generated by the post-translational modification of glutamyl (Glu) residues. These Gla residues induce a conformational change from a 3 10 helix to an alpha helix on binding to Calcium. In the broader scheme of genetic conotoxin classification, Conanotokins are also known as "Conotoxin Superfamily B." The word "conantokin" is derived from the Filipino word antokin, meaning sleepy. Subtypes Conantokin are in general named after the specific epithet of the Conus species it is found in, using single-letter abbreviations if possible. A conantokin from Conus radiatus is called Conantokin-R, but the latter-discovered ones from Conus rolani are called Canontokin-Rl. If a species makes multiple conantokins, numbers or letters are suffixed to the names. The abbreviation for "Conantokin" in these names is always "Con". Conantokin-G Also known as the “sleeper peptide” or CGX-1007, Con-G () is a small peptide isolated from the fish-hunting snail, Conus geographus. It is the best-characterized conantokin, and acts as a functional inhibitor of NMDAR. 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 blocks NMDAR-mediated excitatory postsynaptic currents (EPSCs). Con-G reduces the strength of excitotoxic intracellular Ca2+ actions and blocks different neuronal injuries in vitro. In certain injuries Con-G shows an exceptional prolongation of the therapeutic window. Con-G can reverse established allodynia and can also fully reverse thermal hypersensitivity induced by nerve injury. Conantokin-T Con-T () is purified from the venom of the fish-hunting cone-snail, Conus tulipa. This peptide has 4 residues of Gla. Con-T acts by inhibiting NMDAR-mediated Ca2+ influx in neurons in the central nervous system. Conantokin-R and -L Con-R () is a highly potent anticonvulsant compound, derived from Conus radiatus. Con-L () is an efficient anticonvulsant compound, derived from Conus lynceus. It differs from Con-R mainly in the C-terminal amino acids and, like Con-R, it induces sleep-like symptoms in