title: Distinct effects of cevimeline and pilocarpine on salivary mechanisms, cardiovascular response and thirst sensation in rats.
abstract: OBJECTIVE
  Cevimeline and pilocarpine (muscarinic receptor agonists) are used as sialogogues in xerostomia treatment. It is important to know the different effects on their salivary mechanisms and the side effects. The aim of the present study was to clarify and compare the comprehensive effects of cevimeline to pilocarpine on salivary, cardiovascular and central mechanisms in rats.
  
  
  METHODS
  Under anaesthesia, whole saliva secretion, parotid blood flow and blood pressure were measured following intra-peritoneal administrations of the sialogogues. In digested parotid cells, intracellular Ca(2+) concentrations were measured after the sialogogue application. In the conscious condition, changes in angiotensin II-induced water intake were observed after cevimeline administration. In the subfornical organ, which is a thirst-related central nucleus, the effect of cevimeline on the neuronal activity was electrophysiologically investigated.
  
  
  RESULTS
  Cevimeline at 80μmolkg(-1) showed slowly increasing and lasting salivation, a similar blood flow increment in the parotid gland and higher pressor response when compared to pilocarpine at 4μmolkg(-1). In parotid cells, cevimeline increased the intracellular Ca(2+) concentration in a similar manner to pilocarpine, but at a higher concentration than pilocarpine. Cevimeline inhibited angiotensin II-induced water intake and neuronal activity in the subfornical organ, which is in contrast to reported effects of pilocarpine.
  
  
  CONCLUSIONS
  Cevimeline activates common salivary mechanism with pilocarpine but has a slower onset of activation, longer duration of salivation and an increased pressor response at higher doses. The anti-dipsogenic effect of cevimeline is due to the inhibitory neuronal effect on the thirst-related central nuclei.
authors.affiliation: Department of Biosciences, Kyushu Dental College, 2-6-1 Manazuru, Kokurakitaku, Kitakyushu, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ono
authors.forename: T
authors.initials: T
authors.lastname: Inagaki
authors.forename: T
authors.initials: T
authors.lastname: Iida
authors.forename: N
authors.initials: N
authors.lastname: Wakasugi-Sato
authors.forename: R
authors.initials: R
authors.lastname: Hosokawa
authors.forename: K
authors.initials: K
authors.lastname: Inenaga
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D004326:Drinking / Q000187:drug effects*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010306:Parotid Gland / Q000187:drug effects; D010862:Pilocarpine / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012472:Salivation / Q000187:drug effects*; D012680:Sensitivity and Specificity; D013356:Subfornical Organ / Q000187:drug effects; D013876:Thiophenes / Q000494:pharmacology*; D013894:Thirst / Q000187:drug effects*
chemical_list: D018721:Muscarinic Agonists; D011812:Quinuclidines; D013876:Thiophenes; D010862:Pilocarpine; C059240:cevimeline