|Title:||Methods for producing analgesia|
|Abstract:||A method of producing analgesia in nociceptive and neuropathic pain is disclosed. The method includes administering to a subject an omega conopeptide which is characterized by its ability to (a) inhibit electrically stimulated contraction of the guinea pig ileum, and (b) bind selectively to omega conopeptide MVIIA binding sites present in neuronal tissue. Also disclosed are novel omega conotoxin peptides effective in producing analgesia.|
|Inventor(s):||Justice; Alan (Sunnyvale, CA), Singh; Tejinder (Palo Alto, CA), Gohil; Kishor Chandra (Richmond, CA), Valentino; Karen L. (San Carlos, CA), Miljanich; George P. (Redwood City, CA)|
|Assignee:||Neurex Corporation (Menlo Park, CA)|
1. A method of producing analgesia in a mammalian subject, comprising
administering to the subject, an omega conopeptide which is effective (a) to inhibit electrically stimulated contraction of the guinea pig ileum, and (b) to bind selectively to omega conopeptide MVIIA binding sites present in neuronal tissue, wherein the activities of the omega conopeptide in inhibition of guinea pig ileum and in binding to the MVIIA binding site are within the ranges of such activities of omega-conotoxins MVIIA and TVIA.
2. The method of claim 1, wherein said activity to bind selectively to omega conopeptide MVIIA binding sites is further evidenced by a selectivity ratio of binding at said MVIIA binding site to binding at a site 2 omega conopeptide binding site which is within the range of selectivity ratios determined for omega conopeptides MVIIA/SNX-111, SNX-199, SNX-236, SNX-239 and TVIA/SNX-185.
3. The method of claim 1, wherein said omega conopeptide is selected from the group consisting of SEQ ID NO: 7 (TVIA/SNX-185), SEQ ID NO: 1 (MVIIA/SNX-111), SEQ ID NO: 30 (SNX-236), SEQ ID NO: 2 (SNX-159), SEQ ID NO: 32 (SNX-239), SEQ ID NO: 33 (SNX-199) and derivatives thereof.
4. The method of claim 1, wherein said administering is to a subject experiencing chronic pain.
5. The method of claim 4, wherein said chronic pain is neuropathic pain.