Significant Increase in Salivary Substance P Level after a Single Oral Dose of Cevimeline in Humans

Abstract EN

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.