High throughput screen utilizing newly discovered intramolecular neuronal calcium channel interactions to discover new analgesics
The present invention relates to compositions to treat Ca V 2 disorders. The invention also relates to methods treating Ca V 2 disorders. The invention further relates to kits for treating Ca V 2 disorders in a subject. The invention further relates to methods of identifying novel treatments for treating Ca v 2 disorders in a subject.
1. A pharmaceutical composition comprising a voltage gated calcium channel modulator comprising an amino acid sequence selected from:
MVRFGDELGGRYGGPGGGERARGGGAGGAGGPGPGGLQPGQRVLYKQSI AQRARTMALYNPIPVKQNCFTVNRSLFVFSEDNVVRKYAKRITEWP (SEQ ID NO: 1); NT B (45-95) KQSIAQRARTMALYNPIPVKQNCFTVNRSLFVFSEDNVVRKYAKRITEWP (SEQ ID NO: 2); or
or NT B (56-95) MALYNPIPVKQNCFTVNRSLFVFSEDNVVRKYAKRITEWP (SEQ ID NO: 3); wherein the modulator is effective to treat ameliorate, reduce or alleviate pain, an analgesic side effect, analgesic tolerance or symptoms thereof and a pharmaceutically acceptable excipient.
2. The pharmaceutical composition of claim 1 , wherein said composition enhances potency of an opioid agonist.
3. The pharmaceutical composition of claim 1 , further comprising an opioid analgesic.
4. The pharmaceutical composition of claim 3 , wherein the opioid analgesic is morphine, hydrocodone, oxycodone, codeine, fentanyl, alfentanil, hydromorphone, meperidine, methadone, oxymorphone, propoxyphene, or tramadol.
5. An isolated peptide consisting of the amino acid sequence SEQ ID NO:1, SEQ Is NO:2, or SEQ ID NO:3.
6. A pharmaceutical composition comprising a voltage gated calcium channel modulator consisting of amino acid sequence: MVRFGDELGGRYGGPGGGERARGGGAGGAGGPGPGGLQPGQRVLYKQSI AQRARTMALYNPIPVKQNCFTVNRSLFVFSEDNVVRKYAKRITEWP (SEQ ID NO: 1); NT B (45-95) KQSIAQRARTMALYNPIPVKQNCFTVNRSLFVFSEDNVVRKYAKRITEWP (SEQ ID NO: 2); or
or NT B (56-95) MALYNPIPVKQNCFTVNRSLFVFSEDNVVRKYAKRITEWP (SEQ ID NO: 3); wherein the modulator is effective to treat, ameliorate, reduce or alleviate pain, an analgesic side effect, analgesic tolerance or symptoms thereof and a pharmaceutically acceptable excipient.
7. A method to treat, ameliorate, reduce or alleviate pain, comprising: administering to a subject in need thereof a pharmaceutically effective amount of a composition of claim 1 or claim 6 .
8. The method of claim 7 , further comprising administering one or more Gβγ polypeptides.
9. The method of claim 7 , further comprising administering one or more opioid agonists.
10. The method of claim 9 , wherein the opioid antagonist is from about 0.1 mg to about 300 mg.
11. The method of claim 7 , wherein the pain is chronic pain, neuropathic pain, or acute pain.
12. A method for enhancing the potency of an opioid agonist comprising administering to a subject in need thereof a therapeutically effective amount of the composition of claim 1 or claim 6 .