Secretion from submucosal salivary glands of the ferret in response to a cholinesterase inhibitor applied onto the oral mucosa

Abstract

Parasympathomimetics or cholinesterase inhibitors taken orally may relieve dry-mouth symptoms, but this route of administration is often associated with adverse systemic reactions. In the present study, an animal model was worked out aimed at stimulating the submucosal glands and avoiding systemic effects. In the anesthetized ferret, saliva from the parotid, sublingual and submandibular glands was prevented from reaching the mouth. Vehicle or physostigmine was applied topically for 10 min on the buccal and labial mucosa on one side, while the other side served as a control. Fluid from each side was collected every 5 min Mean basal secretion was 0.17 mg 5 min(-1). The response to physostigmine 0.1% did not exceed that of the vehicle. At higher concentrations the responses lasted 80-120 min. Peak secretion was nine (0.25% physostigmine), 13 (0.5% physostigmine) and 40 (1% physostigmine) times higher than baseline. At 1% physostigmine, the secretion from the control side was elevated, and a small flow from the duct-cannulated parotid gland occurred, indicating systemic effects. Arterial blood pressure was well maintained. Additional observations on the duct-cannulated zygomatic gland showed that secretion from this gland increased already within the 10-min period of application of physostigmine to the overlying mucosa. The distance between the mucosa and the zygomatic gland was only about 1 mm. Physostigmine-induced secretion was abolished by atropine. Local gland stimulation may be an attractive alternative for the treatment of dry mouth.

The cholinesterase inhibitor physostigmine for the local treatment of dry mouth: a randomized study

“…However, a certain contribution by the major glands to the volume of saliva cannot be excluded and in fact seems likely at the dose levels of physostigmine associated with systemic cholinergic adverse effects. This idea gains support from our previous animal studies, where the buccal mucosa was exposed to increasing concentrations of physostigmine and the ducts of the major glands were cannulated to detect any systemically elicited flow of saliva (7).…”

“…Animal studies have revealed that the reversible cholinesterase inhibitor physostigmine, applied locally to the oral mucosa, causes secretion from cholinergically innervated submucosal glands (7, 8). Physostigmine, a tertiary amine, transverses the mucosal layer and prevents the degradation of acetylcholine, released from the intraglandular cholinergic nerve endings, thus enhancing the cholinergic tone of the secretory cells (7, 8).…”

World Workshop on Oral MedicineVI: a systematic review of medication‐induced salivary gland dysfunction

“…It has been shown that following topical application to the oral mucosa, the acetylcholinesterase inhibitor physostigmine will diffuse through the epithelium to stimulate indirectly underlying minor salivary glands, by preventing the breakdown of acetylcholine released from parasympathetic nerve endings. This alleviates symptoms of xerostomia for 2–3 h without producing systemic effects (Hedner et al , ; Ekström & Helander, ; Khosravani et al , ).…”

Atypical antipsychotics – effects of amisulpride on salivary secretion and on clozapine‐induced sialorrhea

“…As judged from the acute salivatory effect of amisulpride currently found, it is tempting to suggest that amisulpride or a molecule related to amisulpride may be developed into a ‘salivation enhancer drug’ to treat dry mouth. A drug of this kind could be applied topically to the oral mucosa with the aim of acting locally on the underlying mucosal mucin‐producing minor salivary glands under cholinergic nerve influence, as is the case for the acetylcholinesterase drug physostigmine (Ekström and Helander, 2002; Khosravani et al , 2009).…”