Saliva secretion rate and saliva composition as a model to determine the effect of antidepressant drugs on cholinergic and noradrenergic transmission.

Three principally different antidepressant drugs--amitriptyline (with effects on both noradrenaline and serotonin reuptake), maprotiline (a selective inhibitor of reuptake of noradrenaline) and zimelidine (a selective inhibitor of reuptake of serotonin) were tested after a single dose and, as concerns maprotiline and zimelidine, after long-term use in healthy volunteers as regards the effects on saliva secretion rate and saliva composition. Amitriptyline gave a strong decrease in both unstimulated and stimulated saliva secretion rate, indicating a strong anticholinergic effect, and a strong increase in the activity of amylase and the content of protein, fucose and hexose in saliva, indicating a strong agonistic effect on noradrenaline transmission. Maprotiline gave an intermediate decrease in saliva secretion rate, and the effect remained after 14 days of treatment. Single doses gave increases in saliva amylase activity and protein content. After 14 days this effect was increased, and there was also a pronounced increase in fucose and hexose content indicating a strong agonistic effect on noradrenaline transmission. Zimelidine gave a low decrease in saliva secretion rate, indicating a mild anticholinergic effect. No certain effect on the saliva composition could be settled after a single dose, but after 14 days there were consistent increases in amylase activity and protein, fucose and hexose content, indicating a facilitation of noradrenaline transmission. Zimelidine as well as its active metabolite, norzimelidine, are selective inhibitors of serotonin reuptake. The action of zimelidine is discussed in view of recent hypotheses about a modulating serotoninergic influence on the noradrenergic system.