Individuals receiving clozapine treatment for schizophrenia complain of drooling. Reports on salivary flow measurements are contradictory in humans and lacking in animals. Clozapine has affinity for several different receptor types and may, hypothetically, both stimulate and inhibit salivary secretion. In rats, intravenous clozapine evoked a long-lasting secretion, being more prominent from submandibular than from parotid glands. Chronic denervation enhanced the responses. Clozapine acted on muscarinic (M1-) receptors of acinar cells, independent of central nervous mechanisms, pre-synaptic intraglandular events, or circulating catecholamines. A fraction of the methacholine- and parasympathetic-nerve-evoked secretion was abolished by clozapine at doses below those evoking secretion. Sympathetic-nerve-evoked secretion was partially reduced by clozapine, due to antagonistic action on α-adrenoceptors; the β-adrenoceptor-mediated response persisted. Subsecretory doses of clozapine enhanced secretion induced by the β-adrenoceptor agonist isoprenaline. The overall actions of clozapine suggest that, in clozapine-treated humans, salivation is increased during sleep and at rest, but is decreased during meals.
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