COMBINATION THERAPY OF LOWER URINARY TRACT DISORDERS WITH α₂δ LIGANDS AND NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)

摘要

The present invention relates to the use of a α₂δ calcium channel subunit ligand and of a non-steroidal anti-inflammatory drug in a combination treatment of a lower urinary tract disorder and the non-steroidal anti-inflammatory drug. The subject of the present invention is the use of the α₂δ calcium channel subunit (A₂d) ligand selected from gabapentin or pregabalin, (1R,5R,6S)-6-aminomethyl-6-carboxymethylbicyclo[3.2.0]heptane, 3-(1-aminomethylcyclohexylmethyl)-4H-1,2,4- oxadiazol-5-one, 5-(1-aminomethylcyclohexylmethyl)-1H-tetrazole, (3S,4S)-(1-aminomethyl-1-carboxymethyl-3,4-dimethylcyclopentane, (1α,3α,5α)-(3-aminomethyl-3-carboxymethylbicyclo[3.2.0]heptane, (3S,5R)-3-aminomethyl-5-methyloctanoic acid, (3S,5R)-3-amino-5-methylheptanoic acid, (3S,5R)-3-amino-5-methyloctanoic acid, (3S,5R)-3-amino-5-methylnonanoic acid, (2S,4S)-4-(3-chlorophenoxy)proline or (2S,4S)-4-(3-fluorobenzyl)proline, or a mixture of two or more thereof in the treatment of urinary incontinence in a subject suffering from a lower urinary tract disorder in combination with the prior, concurrent or post-administration of a non-steroidal anti-inflammatory drug (NSAID). Another subject of the invention is the use of the non-steroidal anti-inflammatory drug in the treatment of urinary incontinence in a subject suffering from a lower urinary tract disorder in combination with the prior, concurrent or post-administration of the α₂δ calcium channel subunit (A₂d) ligand selected from gabapentin or pregabalin, (1R,5R,6S)-6-aminomethyl-6-carboxymethylbicyclo[3.2.0]heptane, 3-(1-aminomethylcyclohexylmethyl)-4H-1,2,4-oxadiazol-5-one, 5-(1-aminomethylcyclohexylmethyl)-1H-tetrazole, (3S,4S)-(1-aminomethyl-1-carboxymethyl-3,4-dimethylcyclopentane, (1α,3α,5α)-(3-aminomethyl-3-carboxymethylbicyclo[3.2.0]heptane, (3S,5R)-3-aminomethyl-5-methyloctanoic acid, (3S,5R)-3-amino-5-methylheptanoic acid, (3S,5R)-3-amino-5-methyloctanoic acid, (3S,5R)-3-amino-5-methylnonanoic acid, (2S,4S)-4-(3-chlorophenoxy)proline or (2S,4S)-4-(3-fluorobenzyl)proline, or a mixture of two or more thereof. Preferably the non-steroidal anti-inflammatory drug is a COX-inhibitor. It is also preferable that the non-steroidal anti-inflammatory drug is celecoxib, diclofenac, diflunisal, flurbiprofen, naproxen, nimesulide or sulindac. One more subject of the invention is the use of compbination of at least one α₂δ calcium channel subunit (A₂d) ligand and at least one non-steroidal anti-inflammatory drug for the concurrent or post-administration in the treatment of urinary incontinence in a subject suffering from a lower urinary tract disorder. Another subject of the invention is the use of the α₂δ calcium channel subunit (A₂d) ligand for the preparation of a medicament for the treatment of urinary incontinence in a subject suffering from a lower urinary tract disorder in combination with the prior, concurrent or post-administration of a non-steroidal anti-inflammatory drug (NSAID). One more subject of the invention is the use of the non-steroidal anti-inflammatory drug for the preparation of a medicament for the treatment of urinary incontinence in a subject suffering from a lower urinary tract disorder in combination with the prior, concurrent or post-administration of the α₂δ calcium channel subunit (A₂d) ligand.