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Mosapride citrate is a novel selective 5-HT4 receptor agonist. It facilitates acetylcholine release from the enteric cholinergic neurons. In contrast to cisapride, mosapride does not block K(+) channels or D2 dopaminergic receptors. The objective of this study is to perform an open study of mosapride citrate's effects on constipation, a prominent lower gastrointestinal tract disorder in parkinsonian patients. A total of 14 parkinsonian patients (7 with Parkinson's disease, 7 with multiple system atrophy; 10 men, 4 women; mean age, 67 years) with constipation (10 with bowel movement3 times/week; 14 with difficulty in defecation) were treated with 15 mg/day of mosapride citrate for 3 months. Pre- and posttreatment objective parameters in colonic transit time (CTT) and rectoanal videomanometry were obtained. Statistical analysis was made by Student's t test. Mosapride was well tolerated by all patients except for 1, who discontinued use of the drug because of epigastric discomfort. None had a worsening of parkinsonism or other adverse events. Thirteen patients reported subjective improvements in bowel frequency (3 times/week, 13) and difficult defecation (13). Mosapride shortened CTT of the left colon (P0.01) and the total colon (P0.05). During rectal filling, mosapride lessened the first sensation (P0.05) and augmented the amplitude in phasic rectal contraction. During defecation, mosapride augmented the amplitude in rectal contraction (P0.05) and lessened the volume of postdefecation residuals. The present study showed for the first time that mosapride citrate augmented lower gastrointestinal tract motility, as shown in CTT and videomanometry, and thereby ameliorated constipation in parkinsonian patients without serious adverse effects.

Both constipation and fecal incontinence are prominent lower gastrointestinal tract (LGIT) dysfunctions that occur frequently in multiple system atrophy (MSA). We investigated the mechanism of constipation and fecal incontinence in MSA. Colonic transit time (CTT), sphincter electromyography (EMG), and rectoanal videomanometry were performed in 15 patients with MSA (10 men, 5 women; mean age, 63.5 years; mean duration of disease, 3 years; decreased bowel frequency [< 3 times a week] in 9; difficulty in expulsion in 11; fecal incontinence in 3) and 10 age-matched healthy control subjects (7 men and 3 women; mean age, 62 years; decreased bowel frequency in 2; mild difficulty in expulsion in 2; fecal incontinence in none). Compared to the control subjects, MSA patients had significantly prolonged CTT in the rectosigmoid segment and total colon. Sphincter EMG showed neurogenic motor unit potentials in none of control subjects but in 93% of MSA patients. At the resting state, MSA patients showed a lower anal squeeze pressure (external sphincter weakness) and a smaller increase in abdominal pressure on coughing. During rectal filling, MSA patients showed smaller amplitude in phasic rectal contraction, which was accompanied by an increase in anal pressure that normally decreased, together with leaking in 3 patients. During defecation, most MSA patients could not defecate completely and had larger postdefecation residuals. MSA patients had weak abdominal strain, smaller rectal contraction on defecation, and larger anal contraction on defecation (paradoxical sphincter contraction on defecation), although these differences were not statistically significant. These findings in MSA patients were similar to those in Parkinson's disease patients in our previous study, except for the sphincter denervation and weakness in MSA. Constipation in MSA most probably results from slow colonic transit, decreased phasic rectal contraction, and weak abdominal strain, and fecal incontinence results from weak anal sphincter due to denervation. The responsible sites for these dysfunctions seem to be both central and peripheral nervous systems that regulate the LGIT.