Secretion from submucosal salivary glands of the ferret in response to a cholinesterase inhibitor applied onto the oral mucosa.
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.
Ekström
Jörgen
J
Department of Pharmacology, Institute of Physiology and Pharmacology, Göteborg, Sweden. jorgen.ekstrom@pharm.gu.se
Helander
Herbert F
HF
D000278:Administration, Buccal; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005289:Ferrets; D005730:Ganglionic Blockers / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D008046:Lip / Q000187:drug effects; D023421:Models, Animal; D009061:Mouth Mucosa / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010306:Parotid Gland / Q000378:metabolism; D014677:Pharmaceutical Vehicles; D010830:Physostigmine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012470:Salivary Glands, Minor / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012636:Secretory Rate / Q000187:drug effects; D013223:Statistics as Topic; D013363:Submandibular Gland / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D005730:Ganglionic Blockers; D018727:Muscarinic Antagonists; D018377:Neurotransmitter Agents; D014677:Pharmaceutical Vehicles; D013373:Substance P; D018738:Hexamethonium; D001285:Atropine; D010830:Physostigmine