Conantokin-L, a new NMDA receptor antagonist: determinants for anticonvulsant potency.
Conantokins are N-methyl-D-aspartate receptor antagonist peptides found in the venoms of marine cone snails. Current intense interest in this peptide family stems from the discovery of their therapeutic potential as anticonvulsants. It was recently reported that conantokin-R is a highly potent anticonvulsant compound, with a protective index of 17.5 when tested in the audiogenic mouse model of epilepsy. Conantokin-L was characterized from Conus lynceus and found to have extensive homology with conantokin-R, except For the C-terminal amino acids. Although conantokin-L appears almost as potent as conantokin-R in standard in vivo assays for conantokins and NMDA receptor binding assays, it is far less potent as an anticonvulsant, with a protective index of 1.2 in the audiogenic mouse model. The results suggest that the C-terminal sequences of conantokin-R and conantokin-L are a major determinant of their anticonvulsant potency.
D000595:Amino Acid Sequence; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002525:Cerebellar Cortex / Q000187:drug effects; D003001:Cloning, Molecular; D020916:Conotoxins; D018076:DNA, Complementary; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010452:Peptide Biosynthesis; D010455:Peptides / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012890:Sleep / Q000187:drug effects; D012908:Snails; D013997:Time Factors
D000927:Anticonvulsants; D020916:Conotoxins; D018076:DNA, Complementary; D018691:Excitatory Amino Acid Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D008978:Mollusk Venoms; D010455:Peptides; D016194:Receptors, N-Methyl-D-Aspartate; C473188:conantokin-L; D016202:N-Methylaspartate