title: In vivo studies of effects of antidepressants on parotid salivary secretion in the rat.
abstract: Tricyclic antidepressants (TCA) are well-known xerogenic drugs, while antidepressants such as selective serotonin reuptake inhibitors (SSRI) are considered less xerogenic. The antimuscarinic effect of the TCAs has been considered to be the principal mechanism causing a dry mouth. Although the muscarinic receptor is commonly targeted by xerogenic pharmaceuticals, the salivation reflex arc may be affected at other levels as well. We currently wondered whether or not antidepressants exert an inhibition of the salivary reflex not only at the glandular level but at a central level as well. In this study, the effects of a TCA (clomipramine), a SSRI (citalopram) and a serotonin-noradrenaline reuptake inhibitor (SNRI; venlafaxine) were examined on reflex- (0.5M citric acid applied on the tongue) and methacholine-evoked salivary secretion. While all three compounds inhibited citric acid-evoked secretion (-40 to -60% at 5mg/kg i.v. of the antidepressants), only clomipramine inhibited methacholine-evoked secretion (-30% at 5mg/kg i.v.). On the contrary, both citalopram and venlafaxine increased the methacholine-evoked secretion (+44 to 49%). This was particularly obvious for the salivary protein output (>200%). In the presence of α- and β-adrenoceptor antagonists, the citalopram- and venlafaxine-induced increases were reduced. Thus, antidepressants irrespective of type may exert xerogenic effects by inhibiting the salivary reflex in the central nervous system. However, while TCAs may also hamper the secretory response by antimuscarinic effects, the SSRI and the SNRI groups of pharmaceuticals seem to lack this additional xerogenic mechanism indicating a better therapeutic profile and better opportunities for pharmacological treatment of drug-induced xerostomia.
authors.affiliation: Department of Pharmacology, the Sahlgrenska Academy at the University of Gothenburg, PO Box 431, SE-405 30 Gothenburg, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Johnsson
authors.affiliation: Department of Pharmacology, the Sahlgrenska Academy at the University of Gothenburg, PO Box 431, SE-405 30 Gothenburg, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Winder
authors.affiliation: Department of Pharmacology, the Sahlgrenska Academy at the University of Gothenburg, PO Box 431, SE-405 30 Gothenburg, Sweden.
authors.forename: Hana
authors.initials: H
authors.lastname: Zawia
authors.affiliation: Department of Oral Diagnostics, Faculty of Odontology, Malmö University, SE-205 06 Malmö, Sweden.
authors.forename: Ida
authors.initials: I
authors.lastname: Lödöen
authors.affiliation: Department of Pharmacology, the Sahlgrenska Academy at the University of Gothenburg, PO Box 431, SE-405 30 Gothenburg, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tobin
authors.affiliation: Department of Oral Diagnostics, Faculty of Odontology, Malmö University, SE-205 06 Malmö, Sweden. Electronic address: bengt.gotrick@mah.se.
authors.forename: Bengt
authors.initials: B
authors.lastname: Götrick
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009420:Nervous System / Q000187:drug effects; D010306:Parotid Gland / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D011941:Receptors, Adrenergic; D012471:Salivary Proteins and Peptides / Q000378:metabolism; D012472:Salivation / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D016210:Methacholine Chloride; D011941:Receptors, Adrenergic; D012471:Salivary Proteins and Peptides; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Citalopram; Clomipramine; Dry mouth; Reflex-evoked saliva; Venlafaxine