title: Significant increase in salivary substance p level after a single oral dose of cevimeline in humans.
abstract: Cevimeline is a novel muscarinic acetylcholine receptor agonist currently being developed as a therapeutic agent for xerostomia. We examined the effects of cevimeline on salivary and plasma levels of substance-P- (SP-), calcitonin-gene-related-peptide- (CGRP-), and vasoactive-intestinal-polypeptide- (VIP-) like immunoreactive substances (ISs) in humans. An open-labeled crossover study was conducted on seven healthy volunteers. Saliva volume was measured, and saliva and venous blood samples were collected before and 30-240 min after a single oral dose of cevimeline or placebo. Salivary and plasma levels of SP-, CGRP-, and VIP-IS were measured using a highly sensitive enzyme immunoassay. A single oral dose of cevimeline resulted in significant increases in salivary but not plasma SP-IS level compared to placebo. Cevimeline administration did not alter the salivary or plasma levels of CGRP-IS or VIP-IS compared to placebo. Significant increases in salivary volume were observed after cevimeline administration compared to placebo. A significant correlation was observed between the total release of SP-IS and that of salivary volume. These findings suggest an association of SP with the enhancement of salivary secretion by cevimeline.
authors.affiliation: Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Oita 879-5593, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Itoh
authors.forename: Kohei
authors.initials: K
authors.lastname: Amada
authors.forename: Ryota
authors.initials: R
authors.lastname: Yamamura
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Sato
authors.forename: Masaharu
authors.initials: M
authors.lastname: Takeyama