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.