Effects of the selective serotonin reuptake inhibitor, fluoxetine, on regional gastric contractility.
Selective serotonin reuptake inhibitors (SSRIs) are increasingly used to treat a variety of disorders but have gastrointestinal side-effects.


OBJECTIVE
To determine the effects of the SSRI, fluoxetine, on gastric smooth muscle contractility.


METHODS
Fundic, antral, and pyloric circular muscle contractility of guinea pig muscle strips were measured in vitro. Fluoxetine was added in concentrations from 0.1 nmol L(-1) to 100 mumol L(-1). Receptor antagonists were used to determine the neural pathways involved.


RESULTS
Fluoxetine caused concentration dependent contractions, which were greatest in fundus compared with the antrum or pylorus. The contractile effects of fluoxetine in the antrum were reduced by tetrodotoxin, atropine, phentolamine, and the 5-HT(4) receptor antagonist GR 113808. The contractile effects of fluoxetine in the fundus were reduced by atropine, phentolamine, and GR 113808.


CONCLUSIONS
Fluoxetine affects gastric contractility with regional variability - contracting the fundus more than the antrum or pylorus. The fluoxetine contractile effect is reduced by tetrodotoxin, atropine, phentolamine, and a 5-HT(4) receptor antagonist. These results suggest fluoxetine interacts with muscarinic, alpha-adrenergic, and serotoninergic receptors and/or ongoing reuptake/release of serotonin in the stomach.
James
A N
AN
Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Ryan
J P
JP
Parkman
H P
HP
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004347:Drug Interactions; D005473:Fluoxetine / Q000494:pharmacology*; D005748:Gastric Fundus / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010646:Phentolamine / Q000494:pharmacology; D011708:Pylorus / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D001285:Atropine; D005473:Fluoxetine; D007211:Indoles; D018727:Muscarinic Antagonists; D010646:Phentolamine; D017981:Receptors, Neurotransmitter; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D013449:Sulfonamides; D013779:Tetrodotoxin; C082871:GR 113808