Salivary secretion effects of the antipsychotic drug olanzapine in an animal model

Abstract

Olanzapine, introduced as an alternative to clozapine in schizophrenia therapy, is thought to display a receptor affinity similar to that of clozapine. Antipsychotics are well-known xerogenic drugs. However, clozapine exerts both antagonistic and agonistic salivary effects ('clozapine-induced sialorrhea'), the latter probably via muscarinic M1 type of receptor. We hypothesise that olanzapine also has dual salivary effects. Effects of intravenous olanzapine were examined in rats, including those subjected to chronic preganglionic parasympathetic denervation (submandibular glands) or combined postganglionic parasympathetic and sympathetic denervation (parotid glands). Secretion was evoked reflexly, and by intravenous methacholine and the tachykinin substance P. At 0.01-1 mg kg(-1), olanzapine dose dependently reduced secretion in response to methacholine or reflex stimulus but not that to substance P. At 10 mg kg(-1), olanzapine evoked a long-lasting secretion, independent of the autonomic innervation as well as of α- and β-adrenergic receptors and muscarinic receptors. The secretion was reduced, but not abolished, by a substance P receptor antagonist. Like clozapine, olanzapine evoked secretion. The response to olanzapine was greater and, in contrast to clozapine, involved non-traditional gland receptors (such as substance P receptors). The findings imply that olanzapine plays an excitatory role via tachykinin receptors in humans.