Comparative Evaluation of Exocrine Muscarinic Receptor Binding Characteristics and Inhibition of Salivation of Solifenacin in Mice

Oki, Tomomi; Takeuchi, Chihiro; Yamada, Shizuo

doi:10.1248/bpb.29.1397

Cited by 22 publications

(11 citation statements)

References 26 publications

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“…Immediately after soaked with saliva, the cotton balls were removed from the mouth and weighed. The volume of saliva was determined gravimetrically, assuming a density of 1 g/ml for saliva [14].…”

Section: Methodsmentioning

confidence: 99%

Restoring the Secretory Function of Irradiation-Damaged Salivary Gland by Administrating Deferoxamine in Mice

Zhang

Cui

et al. 2014

PLoS ONE

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ObjectivesOne of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO) to restore the secretory function of radiation-damaged salivary glands in mice.MethodsDFO (50 mg/kg/d) was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy) of submandibular glands. The total 55 mice were randomly divided into: (1) Normal group: mice received no treatment (n = 5); (2) Irradiation group (IR): mice only received irradiation (n = 5); (3) Pre-DFO group (D+IR) (n = 10); (4) Pre+Post DFO group (D+IR+D) (n = 10); (5) Post-DFO group (IR+D) (n = 10); (6) For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved) for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5); sham2: Pre+Post sterilized water group (n = 5); sham3: Post-sterilized water group (n = 5). The salivary flow rate (SFR) was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations.ResultsThe salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR.ConclusionsOur results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and more preserved stem cells.

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Section: Methodsmentioning

confidence: 99%

Restoring the Secretory Function of Irradiation-Damaged Salivary Gland by Administrating Deferoxamine in Mice

Zhang

Cui

et al. 2014

PLoS ONE

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“…Although solifenacin has shown greater selectivity for urinary bladder over salivary gland than other antimuscarinic agents in both in vitro and in vivo studies, the reason for this difference may be difficult to explain in terms of muscarinic receptor-subtype selectivity only. The inhibitory effect of solifenacin on salivary secretion was recently reported to be weaker than that of oxybutynin in mice, due to solifenacin's slower receptor binding kinetics of association and lower binding activity than oxybutynin (17,18). In addition, solifenacin dissociates more readily from muscarinic receptors in the mouse submaxillary gland than oxybutynin, which is also considered to contribute to its weak inhibitory effect on salivary secretion.…”

Section: In Vivomentioning

confidence: 99%

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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“…Studies on the mouse have compared some prescribed anticholinergics used in the treatment of overactive bladders -oxybutynin, solifenacin and tolterodine. Submandibular gland secretion was less affected by solifenacin and tolterodine compared to oxybutynin, and solifenacin dissociated from muscarinic receptors more easily than oxybutynin [ 57 ].…”

Section: Efferent Signalling and Muscarinic Receptor Antagonistsmentioning

confidence: 85%

Medication-Induced Dry Mouth

Proctor

2014

Dry Mouth

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A wide range of medications have been found to be associated with xerostomia, the subjective symptom of dry mouth. The assessment of medication-induced xerostomia (MIX) is usually made through a subject's responses to relevant questions or the use of visual analogue scales whereby the subject is asked to rate the severity of their oral dryness. It is uncertain how much MIX is accompanied or can be ascribed to medication-induced salivary gland hypofunction and reduced secretion of saliva. MIX in older age groups is associated with the number of medications being taken and is higher than seen in the younger subjects. Many medications cause xerostomia as a side effect, but some of these, for example, selective serotonin reuptake inhibitors, do not appear to cause salivary gland hypofunction. However, there have been relatively few studies assessing objective changes in salivary fl ow in response to medications. The salivary refl ex has peripheral and central components which can be the targets of medications, leading to interruption of the refl ex and medication-induced salivary gland dysfunction (MISGD) characterized by reduced production of saliva. The principal peripheral target is the cholinergic muscarinic (M3) receptor of salivary gland acinar cells which is blocked by antimuscarinic drugs used in the treatment of, for example, irritable bladder and chronic obstructive pulmonary disease. Tricyclic antidepressants not only have targets in the central nervous system but interact with and block muscarinic receptors in the periphery. Sympathetic nervemediated stimuli enhance salivary secretion, and there is no peripheral inhibition. Although adrenergic antagonists cause MIX, there is no evidence that they reduce salivary secretion. However, antihypertensive β-adrenoceptor blockers

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Comparative Evaluation of Exocrine Muscarinic Receptor Binding Characteristics and Inhibition of Salivation of Solifenacin in Mice

Cited by 22 publications

References 26 publications

Restoring the Secretory Function of Irradiation-Damaged Salivary Gland by Administrating Deferoxamine in Mice

Restoring the Secretory Function of Irradiation-Damaged Salivary Gland by Administrating Deferoxamine in Mice

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

Medication-Induced Dry Mouth

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