fluvoxamine and mosapride

It was recently reported that activation of enteric neural 5-HT(4) receptors (SR4) promotes reconstruction of enteric neural circuit injury in distal gut of guinea pigs and that this reconstruction involves neural stem cells. We aimed to explore a novel approach using a selective serotonin reuptake inhibitor (SSRI), which increases endogenous 5-HT, to repair enteric nerve fiber injury in the rat distal gut. Enteric nerve fiber injury was performed by rectal transection and subsequent end-to-end one-layer anastomosis. The SSRI fluvoxamine maleate (100 μmol/l) was applied locally at the anastomotic site to compare with the 5-HT(4) agonist mosapride citrate (100 μmol/l) (applied for patent) applied locally and orally. Unlike mosapride, fluvoxamine failed to promote the regeneration of the nerve fiber tract across the anastomosis. Furthermore, fluvoxamine did not generate anti-distal-less homeobox 2 (DLX2)- and anti-SR4-positive cells (neural stem cells) and/or anti-neurofilament (NF)-positive cells (neural cells) in newly formed granulation tissue at the anastomosis, whereas these cell types were observed in mosapride-treated preparations. In contrast to its effects in guinea pigs, mosapride generated 5-bromo-2'-deoxyuridine (BrdU)-positive neural cells in ganglia sites 3 mm oral and anal from the anastomosis 2 wk after nerve fiber injury. All actions of mosapride were observed after local and or oral applications. These findings indicate that local SSRI treatment does not induce in vivo nerve fiber tract growth across the anastomosis in the rat distal gut. Mosapride induces nerve fiber tract growth across the anastomosis, mediated through enteric neural stem cells possibly from neural crest-derived stem cells or mesenchymal stem cells in the bone marrow.

Topics: Administration, Topical; Anastomosis, Surgical; Animals; Benzamides; Defecation; Fluvoxamine; Guinea Pigs; Male; Morpholines; Nerve Fibers; Neurogenesis; Rats; Rectum; Selective Serotonin Reuptake Inhibitors; Serotonin 5-HT4 Receptor Agonists

We investigated the association between fluvoxamine and nausea from various viewpoints. The incidence of nausea induced by fluvoxamine was 29% (12/41). Plasma 5-hydroxyindoleacetic acid (p5-HIAA) levels after fluvoxamine administration were significantly higher in patients with nausea (6.6+/-3.4 ng/ml) than in those without nausea (3.5+/-2.7 ng/ml). On the other hand, no significant differences were found between patients with and patients without nausea in terms of sex, age, initial and maximum dosages of fluvoxamine and its plasma concentrations, and clinical response to fluvoxamine. However, the incidence of nausea in patients who were initially administered fluvoxamine at under 50 mg/day was significantly lower than in those who were started at above 50 mg/day. In addition, mosapride, a member of the benzamide family, was effective in alleviating fluvoxamine-induced nausea. These results suggest that fluvoxamine-induced nausea is associated with hyperactivity in serotonergic neurons.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Benzamides; Depressive Disorder, Major; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Hydroxyindoleacetic Acid; Male; Middle Aged; Morpholines; Nausea; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index