title: Atypical antipsychotics--effects of amisulpride on salivary secretion and on clozapine-induced sialorrhea.
abstract: OBJECTIVE
  Amisulpride is suggested for treatment of clozapine-induced sialorrhea. However, objective measurements of its effectiveness are lacking and, preclinically, amisulpride has no effect. We currently hypothesise that amisulpride acts by reducing the nervous- rather than the clozapine-driven salivary secretion.
  
  
  METHODS
  Effects of intravenous amisulpride (as well as of clozapine and raclopride, a dopamine D2/D3 antagonist) were investigated in rats, including those subjected to chronic preganglionic parasympathetic denervation (submandibular glands) or combined postganglionic parasympathetic and sympathetic denervation (parotid glands). In duct-cannulated glands, secretion was evoked reflexly, at low and maximum flow rates, and by electrical stimulation of the parasympathetic and sympathetic innervations, and administration of autonomimetics (including substance P).
  
  
  RESULTS
  Unlike clozapine, amisulpride had no effect on the reflexly evoked secretion at maximum rate. With respect to reflex secretion at low rate and to the secretion evoked by muscarinic, α-adrenergic, β-adrenergic and substance P receptors, amisulpride (in contrast to raclopride) dose dependently potentiated the responses. Amisulpride had no effect on gland blood flow.
  
  
  CONCLUSIONS
  No support for any inhibitory influence of amisulpride was found. Conversely, amisulpride universally enhanced secretion, suggesting that amisulpride is a potential drug for dry-mouth treatment. The mechanism behind the potentiation is currently unknown.
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Godoy
authors.forename: A
authors.initials: A
authors.lastname: Riva
authors.forename: J
authors.initials: J
authors.lastname: Ekström
mesh_terms: D000077582:Amisulpride; D000681:Amylases / Q000032:analysis; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001337:Autonomic Agents / Q000494:pharmacology; D018723:Bethanechol / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003714:Denervation; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010306:Parotid Gland / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012463:Saliva / Q000201:enzymology / Q000378:metabolism; D012472:Salivation / Q000187:drug effects*; D012798:Sialorrhea / Q000139:chemically induced; D013363:Submandibular Gland / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D001337:Autonomic Agents; D018723:Bethanechol; D016210:Methacholine Chloride; D013373:Substance P; D020891:Raclopride; D013469:Sulpiride; D000077582:Amisulpride; D000681:Amylases; D003024:Clozapine; D007545:Isoproterenol