Effects of clozapine on human labial salivary glands. An ultrustructural study

Clozapine is a dibenzodiazepine derivative used in psycotic patients treatment resistant that has antagonistic activity at some muscarinic (M1, M5), and alpha2 adrenergic receptors, while it acts as selective agonist at M4 receptors. To study clozapine-induced hypersalivation, one of its most important side effects, we have investigated the morphological effect of clozapine on human labial salivary glands. Human labial are tubulo-alveolar glands with mostly mucous and a few seromucous units and are said to be only under muscarinic control. Slices were stimulated in vitro with Clozapine (10µM) and Atropine (20µM) plus Clozapine (10 µM). Specimens were fixed, embedded in epoxy resin for TEM and LM and subjected to our OsO4 maceration method for HRSEM. In human labial glands, clozapine causes secretion particularly in mucous cells which often present, by LM and TEM, large irregular lumina full of mucus, and evident profiles of exocytosis. Here, cells have cuboidal form and the cytoplasm is reduced to a minimum. Sometimes, however, high stimulated acini are seen close to unstimulated ones. Seromucous cells present a number of granules in their apical portion with sings of exocytosis. By SEM, there are images of active discharge while lumina are full of dense mucus. In specimens treated with atropine plus clozapine, cells still show images of exocytosis, confirming that the drug-induced hypersalivation may be due to the stimulation of other receptors beside the muscarinic ones. Our morphological findings may improve the knowledge of clozapine-induced hypersalivation and the prevention of this side effect