Synergistic combinations of an alpha-2-delta ligand and a cGMP phosphodieterse 5 inhibitor
The instant invention relates to a combination of an alpha-2-delta ligand and a PDEV inhibitor for use in therapy, particularly in the treatment of pain, particularly neuropathic pain. Particularly preferred alpha-2-delta ligands are gabapentin and pregabalin. A particularly preferred PDEV inhibitors is sildenafil.
1. A combination consisting essentially of an alpha-2-delta ligand selected from gabapentin, pregabalin or a pharmaceutically acceptable salt or solvate thereof; and a PDEV inhibitor selected from: 5-[2-ethoxy-5-(4-methyl-1-piperazinylsulphonyl)phenyl]-I-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (sildenafil) or a pharmaceutically acceptable salt or solvate thereof; the alpha-2 delta ligand and the PDEV inhibitor being present in a ratio from 1:1 to 10:1 by weight.
2. A combination according to claim 1 wherein the alpha-2-delta ligand is gabapentin, or a pharmaceutically acceptable salt or solvate thereof.
3. A combination according to claim 1 , wherein the alpha-2-delta ligand is gabapentin, or a pharmaceutically acceptable salt or solvate thereof.
4. A method of treating pain, the method comprising administering to a subject in need thereof a therapeutically effective amount of a combination consisting essentially of an alpha-2-delta ligand selected from gabapentin, pregabalin or a pharmaceutically acceptable salt or solvate thereof; and a PDEV inhibitor selected from: 5-[2-ethoxy-5-(4-methyl-1-piperazinylsulphonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (sildenafil); or a pharmaceutically acceptable salt or solvate thereof; the alpha-2 delta ligand and the PDEV inhibitor being present in a ratio from 1:10 to 20:1 1:1 to 10:1 by weight.
5. A method according to claim 4 , wherein the alpha-2-delta ligand is gabapentin, or a pharmaceutically acceptable salt or solvate thereof.
6. A method according to claim 4 wherein the alpha-2-delta ligand is pregabalin, or a pharmaceutically acceptable salt or solvate thereof.