Clozapine: agonistic and antagonistic salivary secretory actions.
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 alpha-adrenoceptors; the beta-adrenoceptor-mediated response persisted. Subsecretory doses of clozapine enhanced secretion induced by the beta-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.
Ekström
J
J
Division of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 13 C, Box 431, SE-405 30 Göteborg, Sweden. jorgen.ekstrom@pharm.gu.se
Godoy
T
T
Riva
A
A
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D017763:Autonomic Denervation; D018678:Cholinergic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D010306:Parotid Gland / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D012463:Saliva / Q000378:metabolism; D012472:Salivation / Q000187:drug effects*; D012798:Sialorrhea / Q000139:chemically induced*; D013363:Submandibular Gland / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism
D014150:Antipsychotic Agents; D018678:Cholinergic Agents; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D003024:Clozapine