The anti-
xerostomia effects of
muscarinic agonists (
cholinomimetics) are reviewed.
Cevimeline (
cevimeline monohydrochloride hemihydrate) is a novel
muscarinic agonist that stimulates salivary secretion in animals and humans both with normal salivary gland function and with impaired salivary secretion (
xerostomia or oral dryness) as effectively as
pilocarpine. Other classic and nonselective
muscarinic agonists, such as
arecoline,
carbachol,
muscarine and
oxotremorine, as well as
acetylcholine, failed to exhibit a sufficient salivation effect even at sublethal doses in animals.Oral administration of
cevimeline 30mg to humans induces a moderate and lasting increase in salivary flow, and the effect is maintained for at least 4 to 6 hours, longer than with
pilocarpine. Mean increases in salivary flow rates after
cevimeline treatment were 2-fold higher than after placebo, and no evidence of tolerance of the pharmacological effect has been observed during prolonged administration for up to 12 months.The clinical efficacy of
cevimeline in relieving symptoms of
xerostomia, including oral dryness and difficulties in chewing, swallowing and speaking, has been demonstrated by placebo-controlled, double-blind, randomised clinical trials in the USA and Japan. In these studies,
cevimeline 30mg three times daily increased salivary flow and improved the symptoms of
xerostomia in a significantly higher percentage of patients compared with placebo. Some patients receiving
cevimeline therapy for
xerostomia experienced adverse events such as sweating, gastrointestinal symptoms (
nausea, diarrhoea,
abdominal pain and
vomiting),
dizziness and rigors; these effects were related to
muscarinic activity and were generally mild and tolerable in comparison with those of
pilocarpine.These findings suggest that
muscarinic M3 agonists are suitable for the treatment of
xerostomia.
Cevimeline in particular has a long-lasting salivation effect with fewer adverse events than
pilocarpine, and so is expected to be more useful for the treatment of
xerostomia in patients with Sjögren's syndrome, reducing symptom severity and improving their quality of life.