Claims
- 1. A method of selecting a compound for use in producing analgesia in a subject, comprising
measuring the ability of said compound to block tetrodotoxin-insensitive (TTXi) sodium channels and to block tetrodotoxin-sensitive (TTXs) sodium channels, and selecting the compound if (i) it exhibits a potency in blocking TTXi sodium channels that is at least about one-tenth as great as the potency exhibited by 3-hydroxy monoethylglycinexylidide in blocking said TTXi sodium channels, and (ii) it exhibits a potency ratio of at least 2 in blocking said TTXi sodium channel as compared to blocking said TTXs sodium channel.
- 2. The method of claim 1, wherein said compound is selected if its potency in inhibiting said TTXi sodium channels is at least as great as that of 3-hydroxy monoethylglycinexylidide in blocking said channels.
- 3. The method of claim 1, wherein said potency ratio of blocking said TTXi and said TTXs sodium channels measured by the formula: 1/(IC50, TTXi/IC50, TTXi) where IC50, TTXi is the concentration of compound effective to inhibit current through said tetrodotoxin-insensitive sodium channel by 50%, and IC50, TTXs is the concentration of said compound effective to inhibit current through said tetrodotoxin-sensitive sodium channel by 50%.
- 4. The method of claim 1, wherein said compound is further monitored for its ability to reversibly block said TTXi sodium channel in a cell bathing solution in an electrophysiological assay of tetrodotoxin-insensitive sodium channels and is selected if not more than 5-15% of a sodium current that passes through said TTXi sodium channel recovers after said compound is removed from said cell bathing solution.
- 5. The method of claim 1, wherein said measuring of tetrodotoxin-insensitive sodium channel blockade is by electrophysiological means.
- 6. The method of claim 1, wherein said measuring of tetrodotoxin-insensitive sodium channel blockade is carried out in a ligand displacement assay.
- 7. The method of claim 6, wherein said ligand is 3-hydroxy monoethylglycinexylidide.
- 8. An analgesic composition, comprising a 3-hydroxy monoethylglycinexylidide analog that (i) is effective to block TTXi sodium channels with a potency that is at least about one-tenth as great as the potency exhibited by 3-hydroxy monoethylglycinexylidide in blocking said channels, and (ii) exhibits a potency ratio of at least 2 in blocking said TTXi sodium channels as compared to blocking TTXs sodium channels.
- 9. The analgesic composition of claim 7, wherein said analog blocks said TTXi sodium channels with a potency that is at least as great as the potency exhibited by 3-hydroxy monoethylglycinexylidide in blocking said channels.
Parent Case Info
[0001] This application is a continuation of U.S. patent application having Ser. No. 08/829,452, filed Mar. 28, 1997, which claims priority to Provisional U.S. Patent Application having Serial No. 60/014,437, filed Mar. 29, 1996, both of which are herein incorporated by reference.
Provisional Applications (1)
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Number |
Date |
Country |
|
60014437 |
Mar 1996 |
US |
Divisions (1)
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Number |
Date |
Country |
Parent |
09454714 |
Dec 1999 |
US |
Child |
10277444 |
Oct 2002 |
US |
Continuations (1)
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Number |
Date |
Country |
Parent |
08829452 |
Mar 1997 |
US |
Child |
09454714 |
Dec 1999 |
US |