title: Parasympathetic vasoactive intestinal peptide (VIP): a likely contributor to clozapine-induced sialorrhoea.
abstract: OBJECTIVE
  The parasympathetic transmitter vasoactive intestinal peptide (VIP) increases salivary gland blood flow and evokes protein secretion and, in some species, such as rats, a small fluid secretion. It interacts synergistically with muscarinics for protein and fluid output. Human salivary acini are supplied with VIP-containing nerves. We hypothesise that VIP and clozapine, acting together, evoke a volume of saliva greater than the sum of those induced by each drug given separately. It was further considered whether, in the current test situation, circulatory events influenced the magnitude of the secretory response.
  
  
  METHODS
  Saliva from parotid glands deprived of their autonomic innervation, and saliva and blood from innervated submandibular glands were collected in adrenoceptor antagonist-pretreated pentobarbitone-anaesthetised rats. Initially, the individual and then the combined effects of intravenous doses of VIP and clozapine were established.
  
  
  RESULTS
  The submandibular volume response to the combination was 2-3 times higher, while blood pressure and glandular blood flow did not differ from those to VIP alone. The synergism occurred independent of nerves as shown in denervated parotid glands.
  
  
  CONCLUSIONS
  From the current preclinical data, we speculate that VIP of parasympathetic origin, by its synergistic interaction with clozapine, may contribute to the clozapine (muscarinic M1-receptor)-induced sialorrhoea in schizophrenics.
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden; Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Ekström
authors.forename: T
authors.initials: T
authors.lastname: Godoy
authors.forename: F
authors.initials: F
authors.lastname: Loy
authors.forename: A
authors.initials: A
authors.lastname: Riva
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003024:Clozapine / Q000009:adverse effects*; D005260:Female; D010275:Parasympathetic Nervous System / Q000378:metabolism; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012798:Sialorrhea / Q000139:chemically induced*; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D014150:Antipsychotic Agents; D014660:Vasoactive Intestinal Peptide; D003024:Clozapine
keywords: clozapine-induced sialorrhoea; salivary secretion; schizophrenia; vasoactive intestinal peptide