Effects of different drugs on the cystometrogram in conscious rats

Guarneri, L.; Cova, Rita; Angelico, Patrizia; Colli, Enrico; Testa, Rodolfo

doi:10.1016/1043-6618(91)90032-s

Cited by 15 publications

(5 citation statements)

References 33 publications

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“…administration. In agreement with previously reported data [9,13,15,16], however, both drugs induced a strong dose-dependent decrease of MP. Furthermore, this behaviour was maintained when a discontinuous cystometry was performed or when different filling rates were utilized.…”

Section: Discussionsupporting

confidence: 93%

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Urodynamic effects of oxybutynin and tolterodine in conscious and anesthetized rats under different cystometrographic conditions

et al. 2005

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Background: Antimuscarinic agents are the most popular treatment for overactive bladder and their efficacy in man is well documented, producing decreased urinary frequency and an increase in bladder capacity. During cystometry in rats, however, the main effect reported after acute treatment with antimuscarinics is a decrease in peak micturition pressure together with little or no effect on bladder capacity. In the present experiments we studied the effects, in rats, of the two most widely used antimuscarinic drugs, namely oxybutynin and tolterodine, utilising several different cystometrographic conditions. The aim was to determine the experimental conditions required to reproduce the clinical pharmacological effects of antimuscarinic agents, as seen in humans, in particular their ability to increase bladder capacity.

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Section: Discussionsupporting

confidence: 93%

“…Despite the favourable results observed in the clinical studies reported above with regard to the cystometrographic modifications induced by treatment with oxybutynin and tolterodine, the only effect generally observed in rats is a decrease in the maximum detrusor pressure at micturition [9-18]. …”

Section: Introductionmentioning

confidence: 99%

Urodynamic effects of oxybutynin and tolterodine in conscious and anesthetized rats under different cystometrographic conditions

et al. 2005

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“…During cystometry in rats, the main effect reported after treatment with antimuscarinics is a decrease in peak micturition pressure, together with little or no effect on bladder capacity [16–22]. The observation that even at 0.01 mg/kg of fesoterodine and SPM 7605 there was a maximal reduction in micturition pressure suggests that the dose range examined was towards the upper end of the dose‐response relationship.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological characterization of a novel investigational antimuscarinic drug, fesoterodine, in vitro and in vivo

et al. 2008

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OBJECTIVE To investigate the primary pharmacology of fesoterodine (a novel antimuscarinic drug developed for treating overactive bladder) and SPM 7605 (its active metabolite, considered to be the main pharmacologically active principle of fesoterodine in man) against human muscarinic receptor subtypes, and to investigate in vitro and in vivo functional activity of these agents on the rat bladder compared with existing standard agents. MATERIALS AND METHODS The displacement of radioligand binding by fesoterodine, SPM 7605 and standard agents in membrane preparations of Chinese hamster ovary (CHO) cells expressing the different human muscarinic receptors (M1–M5) was characterized. Agonistic and antagonistic activities were studied using different CHO cell lines stably expressing the human recombinant muscarinic receptor subtypes. The effects of fesoterodine and SPM 7605 on isolated bladder strips contracted by carbachol or electrical field stimulation (EFS) were investigated. In vivo the effects of fesoterodine and SPM 7605 on micturition variables were assessed using continuous cystometry in conscious female Sprague‐Dawley rats, and compared to those of oxybutynin and atropine. RESULTS In vitro SPM 7605 potently inhibited radioligand binding at all five human muscarinic receptor subtypes with equal affinity across all five. Fesoterodine had a similar balanced selectivity profile but was less potent than SPM 7605. Both substances were competitive antagonists of cholinergic agonist‐stimulated responses in human M1‐M5 cell lines and had a similar potency and selectivity profile to the radioligand‐binding studies. In rat bladder strips, fesoterodine and SPM 7605 caused a rightward shift of the concentration‐response curve for carbachol with no depression of the maximum, and concentration‐dependently reduced contractions induced by EFS. The potency of both drugs was similar to that of atropine and oxybutynin. In the presence of the esterase inhibitor neostigmine, the concentration‐response curve of fesoterodine was shifted to the right, suggesting that part of the activity was caused by metabolism to SPM 7605 by tissue enzymes. In vivo, low doses (0.01 mg/kg) of fesoterodine and SPM 7605 reduced micturition pressure and increased intercontraction intervals and bladder capacity, but did not affect residual volume. CONCLUSIONS Fesoterodine and its active metabolite, SPM 7605, are nonsubtype selective, competitive antagonists of human muscarinic receptors, but SPM 7605 has greater potency than the parent compound. Pharmacodynamic studies in the rat bladder in vitro confirm the competitive muscarinic antagonist profile of these agents in a native tissue preparation, and in vivo studies in the rat showed effects on bladder function consistent with a muscarinic antagonist profile.

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“…Moreover, Sasaki et al (23) reported that oxybutynin decreased the micturition pressure in both sham-operated and nervetransected rats without increasing the bladder capacity. Moreover, Guarneri et al (24,25) found the decrease of micturition pressure without effect on bladder capacity. These reports accorded with our findings that oxybutynin decreased the pressure of rhythmic urinary bladder contraction.…”

Section: Discussionmentioning

confidence: 99%

Effects of 4-Ethylamino-2-butynyl(2-cyclohexyl-2-phenyl)glycolate Hydrochloride, a Metabolite of Oxybutynin, on Bladder Specimens and Rhythmic Bladder Contraction in Rats in Comparison With Oxybutynin

et al. 2004

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Abstract. Oxybutynin has been used for neurogenic bladder disorders and is known to have anti-cholinergic and antispasmodic properties. However, the anti-cholinergic and antispasmodic properties of 4-ethylamino-2-butynyl(2-cyclohexyl-2-phenyl)glycolate hydrochloride (N-desethyloxybutynin: DEOB), a metabolite of oxybutynin, have not been clarified. Therefore, in the present study, we studied these properties by using rat urinary bladder specimens in comparison with oxybutynin. Moreover, the effect of DEOB on rhythmic urinary bladder contraction was also evaluated using anesthetized rats. DEOB and oxybutynin concentration-dependently inhibited the carbachol-induced contraction, the pA 2 values being 7.19 and 7.11, respectively. DEOB and oxybutynin also concentration-dependently inhibited the 100 mM KCl-induced contraction, the ED 50 values being 12.1 and 10.4 mM, respectively. Intravenously administered DEOB and oxybutynin dose-dependently (0.03 -0.3 mg / kg) inhibited the amplitude of the rhythmic bladder contraction to similar degrees, but had no affect on the frequency. From the above results, it was determined that DEOB has anti-cholinergic and antispasmodic properties and that these activities were almost equal to those of oxybutynin. Therefore, DEOB may play an important role during oxybutynin therapy for neurogenic bladder disorder.

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Effects of different drugs on the cystometrogram in conscious rats

Cited by 15 publications

References 33 publications

Urodynamic effects of oxybutynin and tolterodine in conscious and anesthetized rats under different cystometrographic conditions

Urodynamic effects of oxybutynin and tolterodine in conscious and anesthetized rats under different cystometrographic conditions

Pharmacological characterization of a novel investigational antimuscarinic drug, fesoterodine, in vitro and in vivo

Effects of 4-Ethylamino-2-butynyl(2-cyclohexyl-2-phenyl)glycolate Hydrochloride, a Metabolite of Oxybutynin, on Bladder Specimens and Rhythmic Bladder Contraction in Rats in Comparison With Oxybutynin

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