Methods for modulating bladder function

Details Methods for modulating bladder function Methods for modulating bladder function

2001-10-15

2002-02-19

Henley, III, Raymond (Department: 1614)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C514S418000, C514S535000

Reexamination Certificate

active

06348486

ABSTRACT:

This invention relates to novel methods for modulating bladder tissues utilizing compounds which modulate the KCNQ family of potassium channels, particularly compounds which open or agonize the channels. The methods of this invention include the treatment, prevention, inhibition and amelioration of urge urinary incontinence also known as bladder instability, neurogenic bladder, voiding dysfunction, hyperactive bladder or detrusor overactivity. The methods of this invention also include the prevention and treatment of mixed stress and urge urinary incontinence, including that associated with secondary conditions such as prostate hypertrophy.
BACKGROUND OF THE INVENTION
U.S. Pat. No. 5,384,330 (Dieter et al.) teaches pharmacologically active 1,2,4-triaminobenzene derivatives of the General Formula:
and their properties as anti-epileptic, muscle relaxing, fever-reducing and peripheral analgesic agents.
U.S. Pat. No. 5,565,483 (Hewawasam et al.) teaches compounds of the formulae:
wherein: R is hydrogen, hydroxy or fluoro; R
1
, R
2
, R
3
and R
4
each are independently hydrogen, C
1-4
alkyl, halogen, trifluoromethyl, phenyl, p-methylphenyl or p-trifluoromethylphenyl; or R
1
and R
2
, R
2
and R
3
or R
3
and R
4
are joined together to form a benzo fused ring; R
5
is hydrogen or C
1-4
alkyl; and R
6
is chlorine or trifluoromethyl; or a nontoxic pharmaceutically acceptable salt, solvate or hydrate thereof, which are potassium channel openers useful for treating ischemia, convulsions and asthma.
The article Modulation of KCNQ2/3 Potassium Channels by the Novel Anticonvulsant Retigabine, Main et al., Molecular Pharmacology, 58: pp. 253-262, 2000, describes the actions of retigabine (D23129; N-[2-amino-4-(4-fluorobenzylamino)-phenyl]carbamic acid ethyl ester) in modulating the KCNQ2/3 potassium channels in oocytes in a 3-fold manner, i.e. retigabine shifts the voltage dependence of channel activation to more hyperpolarized membrane potentials, increases the rate of channel activation and slows channel deactivation.
U.S. Pat. Nos. 5,849,789 and 5,852,053 (both to Rostock et al.) teaches the use of retigabine for the treatment of neurodegenerative disorders, including those associated with stroke.
U.S. Pat. No. 5,914,425 (Meisel et al.) teaches novel crystalline forms of retigabine.
U.S. Pat. No. 6,117,900 teaches the use of retigabine, also known as N-[2-amino4-(4-fluorobenzylamino)-phenyl]carbamic acid ethyl ester, for the treatment of neuropathic pain.


REFERENCES:
patent: 5384330 (1995-01-01), Dieter et al.
patent: 5565483 (1996-10-01), Hewawasam et al.
patent: 5849789 (1998-12-01), Rostock et al.
patent: 5852053 (1998-12-01), Rostock et al.
patent: 5914425 (1999-06-01), Meisel et al.
patent: 6117900 (2000-09-01), Rundfeldt
Martin J. Main et al., Molecular Pharmacology, 2000, 253-262, 58.
Rikke Louise Schroder et al., Neuropharmacology, 2001, 888-898, 40.

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