Atypical antipsychotics - effects of amisulpride on salivary secretion and on clozapine-induced sialorrhea

• Published in: Oral diseases 2012-10, Vol.18 (7), p.680-691
• Main Authors: Godoy, T, Riva, A, Ekström, J
• Format: Article
• Language: English
• Subjects: 1980; 1989; 1994; amisulpride; Amylases - analysis; Animals; Antipsychotic Agents - pharmacology; atypical antipsychotics; Autonomic Agents - pharmacology; Bethanechol - pharmacology; blood-flow; carthy rh; Clozapine - pharmacology; clozapine-induced sialorrhea; Denervation; Dentistry; dopamine; ernick w; european journal of pharmacology; Female; in-vivo; induced hypersalivation; Isoproterenol - pharmacology; journal of clinical psychopharmacology; journal of dental research; medicine; Methacholine Chloride - pharmacology; n-desmethylclozapine; Neurologi; Neurology; ntaine j; Odontologi; p281; p55; p59; Parasympathetic Nervous System - drug effects; Parotid Gland - drug effects; Parotid Gland - innervation; Parotid Gland - secretion; Raclopride - pharmacology; rat parotid-gland; Rats; Rats, Sprague-Dawley; reflex secretion; Saliva - enzymology; Saliva - secretion; salivary secretion; Salivation - drug effects; schizophrenia; Sialorrhea - chemically induced; stimulation; Submandibular Gland - blood supply; Submandibular Gland - drug effects; Submandibular Gland - innervation; Submandibular Gland - secretion; Substance P - pharmacology; substituted benzamides; Sulpiride - analogs & derivatives; Sulpiride - pharmacology; Sympathetic Nervous System - drug effects; v14; v68
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/j.1601-0825.2012.01926.x

Oral Diseases (2012) 18, 680–691 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. Material and 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.