Effect of antimuscarinic drugs used for overactive bladder on learning in a rat passive avoidance response test

Suzuki, Michitaka; Noguchi, Yukiko; Okutsu, Hiroko; Ohtake, Akiyoshi; Sasamata, Masao

doi:10.1016/j.ejphar.2006.11.054

Cited by 27 publications

(16 citation statements)

References 24 publications

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“…Although the affinity of solifenacin for the M 3 receptor is only marginal over that for the M 1 -receptor subtype, solifenacin was scarcely detected in the brain of rats, indicating that it does not penetrate the blood-brain barrier (10). In addition, it was confirmed that solifenacin does not affect learning function in a passive avoidance task in rats (11). Adverse effects such as impairment of cognitive functions are therefore considered of little concern.…”

Section: Effects On Muscarinic Receptorsmentioning

confidence: 49%

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Ameliorative Effect of Solifenacin Succinate (Vesicare®), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especially Urgency Episodes

et al. 2010

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Abstract. Overactive bladder (OAB) syndrome is a common condition that is most often observed in the elderly. Pharmacological treatment with muscarinic receptor antagonists has been most widely used for OAB. An antimuscarinic agent, solifenacin, showed the highest affinity for the muscarinic M 3 receptor, which mediates urinary bladder contraction. In preclinical studies, solifenacin exhibited a highly bladder-selective profile compared with other antimuscarinic agents. Solifenacin was also shown to increase bladder capacity without affecting residual urine in an OAB model of rats. Urgency is now considered to result from overactivation of afferent nerves from the urinary bladder. It has been reported that afferent nerves are located adjacent to the urothelium, and stimulation of muscarinic receptors expressed on the urothelium may contribute to the activation of afferent nerves via non-neuronal ATP release. Solifenacin produces its inhibitory effect on bladder afferent activity partly via the suppression of non-neuronal ATP release. Clinically, solifenacin ameliorates all symptoms in OAB patients; and in particular, it produces a significant decrease in urgency episodes, which is the principal symptom of OAB. The pharmacological profile of solifenacin is therefore considered to contribute to its beneficial effects of high efficacy against OAB symptoms with good tolerability.

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Section: Effects On Muscarinic Receptorsmentioning

confidence: 49%

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Ameliorative Effect of Solifenacin Succinate (Vesicare®), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especially Urgency Episodes

et al. 2010

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“…The i.v. doses of oxybutynin (0.1-1.0 mg/kg), darifenacin (0.1-1.0 mg/kg) and imidafenacin (0.01-0.1 mg/kg) used herein were pharmacologically relevant (Suzuki et al 2007;Ohno et al 2008). The plasma concentration of imidafenacin at these doses was similar to (0.01 mg/kg) or 10 fold higher (0.1 mg/kg) than that in patients receiving an oral dose of 0.1 mg of imidafenacin (Ohno et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Noninvasive evaluation of brain muscarinic receptor occupancy of oxybutynin, darifenacin and imidafenacin in rats by positron emission tomography

et al. 2010

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“…In contrast, darifenacin at pharmacologically effective doses did not significantly reduce in vivo specific [ 11 C](+)3-MPB binding so that the RO 50 value could not be estimated. RO 50 values of antimuscarinic agents were similar to intravenous doses inhibiting learning/memory behavior in rats (63). Thus, these values could be regarded as the index of CNS pharmacological effects following the blockade of brain muscarinic receptors.…”

Section: Muscarinic Receptor Selectivity In the Bladder Over The Brainmentioning

confidence: 82%

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Bladder Selectivity Based on In Vivo Drug–Receptor Binding Characteristics of Antimuscarinic Agents for Treatment of Overactive Bladder

et al. 2010

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Abstract.We have reviewed the binding of antimuscarinic agents, used to treat urinary dysfunction in patients with overactive bladder, to muscarinic receptors in target and non-target tissues in vivo. Transdermal administration of oxybutynin in rats led to significant binding in the bladder without long-term binding in the submaxillary gland and the abolishment of salivation evoked by oral oxybutynin. Oral solifenacin showed significant and long-lasting binding to muscarinic receptors in mouse tissues expressing the M 3 subtype. Oral tolterodine bound more selectively to muscarinic receptors in the bladder than in the submaxillary gland in mice. The muscarinic receptor binding activity of oral darifenacin in mice was shown to be pronounced and long-lasting in the bladder, submaxillary gland, and lung. In vivo quantitative autoradiography using (+) N -[11 C] methyl-3-piperidyl benzilate in rats showed significant occupancy of brain muscarinic receptors on intravenous injection of oxybutynin, propiverine, solifenacin, and tolterodine. The estimated in vivo bladder selectivity compared to brain was significantly greater for solifenacin and tolterodine than oxybutynin. Darifenacin occupied few brain muscarinic receptors. Similar findings were also observed with positron emission tomography in conscious rhesus monkeys. The newer generation of antimuscarinic agents may be advantageous in the bladder selectivity after systemic administration.

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Effect of antimuscarinic drugs used for overactive bladder on learning in a rat passive avoidance response test

Cited by 27 publications

References 24 publications

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Ameliorative Effect of Solifenacin Succinate (Vesicare®), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especially Urgency Episodes

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Ameliorative Effect of Solifenacin Succinate (Vesicare®), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especially Urgency Episodes

Noninvasive evaluation of brain muscarinic receptor occupancy of oxybutynin, darifenacin and imidafenacin in rats by positron emission tomography

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Bladder Selectivity Based on In Vivo Drug–Receptor Binding Characteristics of Antimuscarinic Agents for Treatment of Overactive Bladder

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