The activity of a recent KATP channel opener, the N-(4-Phenylsulfonylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide (ZM226600) was investigated on a female rat model of overactive bladder with outlet obstruction. Both ZM226600 and pinacidil instilled into the bladder (10-7 M, 30 min) or following systemic administration (10, 100 nmol/kg e.v.) almost completely abolished bladder overactivity and improved residual volume and frequency of micturition. However, pinacidil affected arterial pressure. Oxybutynin instilled into the bladder (10 -7, 10-6, 10-5 M, 30 min) decreased detrusor overactivity by about 16%, 25% and 46% respectively, but also blocked micturition reflexes at highest doses tested. Oxybutynin reduced detrusor overactivity by about 50% and 80%, after systemic administration (10, 100 nmol/kg e.v.), but also blocked micturition reflexes at the highest dose tested. In conclusion, ZM226600 is more active than oxybutynin in reducing bladder overactivity, and it is devoid of vascular side effects observed with pinacidil. Its short duration of action (about 1 h) is probably the main problem to solve, in order to consider this compound a valid alternative to antimuscarinics in the therapy of bladder overactivity. (copyright) 2005 Elsevier B.V. All rights reserved.

Effect of the ATP-sensitive potassium channel opener ZM226600 on cystometric parameters in rats with ligature-intact, partial urethral obstruction / C. Pinna, L. Puglisi, P. Sanvito, C. Bolego, A. Cignarella. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - 516:1(2005), pp. 71-77. [10.1016/j.ejphar.2005.04.011]

Effect of the ATP-sensitive potassium channel opener ZM226600 on cystometric parameters in rats with ligature-intact, partial urethral obstruction

C. Pinna
Primo
;
L. Puglisi;C. Bolego
Penultimo
;
A. Cignarella
Ultimo
2005

Abstract

The activity of a recent KATP channel opener, the N-(4-Phenylsulfonylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide (ZM226600) was investigated on a female rat model of overactive bladder with outlet obstruction. Both ZM226600 and pinacidil instilled into the bladder (10-7 M, 30 min) or following systemic administration (10, 100 nmol/kg e.v.) almost completely abolished bladder overactivity and improved residual volume and frequency of micturition. However, pinacidil affected arterial pressure. Oxybutynin instilled into the bladder (10 -7, 10-6, 10-5 M, 30 min) decreased detrusor overactivity by about 16%, 25% and 46% respectively, but also blocked micturition reflexes at highest doses tested. Oxybutynin reduced detrusor overactivity by about 50% and 80%, after systemic administration (10, 100 nmol/kg e.v.), but also blocked micturition reflexes at the highest dose tested. In conclusion, ZM226600 is more active than oxybutynin in reducing bladder overactivity, and it is devoid of vascular side effects observed with pinacidil. Its short duration of action (about 1 h) is probably the main problem to solve, in order to consider this compound a valid alternative to antimuscarinics in the therapy of bladder overactivity. (copyright) 2005 Elsevier B.V. All rights reserved.
animal model; animal tissue; arterial pressure; article; controlled study; cystometry; detrusor muscle; dose response; drug megadose; female; nonhuman; overactive bladder; potassium channel; priority journal; rat; residual volume; urethra stenosis; urinary frequency; n (4 phenylsulfonylphenyl) 3,3,3 trifluoro 2 hydroxy 2 methylpropionamide; oxybutynin; pinacidil; potassium channel stimulating agent; propionamide derivative; unclassified drug; zm 226600; zm 226600
Settore BIO/15 - Biologia Farmaceutica
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/6561
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