Physiological Activity And Analgesic Pharmacology Of Several New Conotoxins

The genus Conus belong to Gastropod Mollusks, and there are nearly 500 in the world. Conotoxins (conopeptides, CTXs) are one kind of the bioactive peptide toxins which are obtained from the genus. Recent researches suggest that, there may be 1000-1900 kinds of conotoxins in each Conus, namely, there are more than 500,000 kinds of conotoxins all of the world, which are ten times of that has been known before. Usually the conotoxins are consisted of 10-46 amino acid residue with disulfide-rich, novel chemical structure, strong biological activity and high selectivity on ion channels or receptors. So far they have been categorized into several superfamilies named A, I, M, O, P, S, and T etc., which are characterized by the number of their cysteine residues. They have been unprecedented attention in the field of neuroscience research and drug development aspects, so it is significant to research conotoxins.The main purpose of this research is to do physiological activity and analgesic pharmacology of new conotoxins synthesized in our laboratory. Young mice and goldfish are used to screen various conopeptides for neurotoxicity activity, and we obtain several conotoxins for analgesic pharmacological test. According to the results above, we chose a-conotoxin LtIA and LvIA to detect their analgesic effect systematicly. Several physical pain models were established, such as hot plate test,tail flick test, formalin test in mice, and chronic constriction injury model in rats which is neuropathic pain model, and make an acute toxicity experiment respectively. At the same time, we tested the insect activity of the two conotoxins. Results:we obtained multiple conotoxins that had biologically active conotoxin, conotoxin LtIA and LvIA show good analgesic activity in the pharmacodynamics experiments, what is more, LvIA showed good insecticide activity. This thesis provide a method and reference for screening analgesic pharmacodynamic candidate drug or drug lead, and provide basis to develop new drugs for neurologic disease.