Alpha 2-adrenergic model of gastroparesis: validation with renzapride, a stimulator of motility.
Motility-stimulating drugs can increase gastric antral and intestinal contractions but do not usually enhance emptying unless gastroparesis is present. An alpha 2-adrenergic agonist (SC-39585A) was used to inhibit antroduodenal motility and simulate gastroparesis in dogs. SC-39585A caused dose-related inhibition of emptying of solid and liquid meals as well as the antral and duodenal motility responses to the solid meal. The motility-enhancing agent renzapride (100 micrograms/kg iv) did not enhance emptying of the solid meal under nondelayed conditions. However, at the same dose it partially reversed the delay in solid emptying but only when antroduodenal motility was incompletely (30 micrograms/kg sc) and not totally (100 micrograms/kg sc) inhibited by SC-39585A. This was done in part by antagonizing antral but not duodenal inhibition of motility. Renzapride was also effective orally in reversing the delay in solid emptying. Similarly, renzapride reversed the delay in liquid emptying caused by SC-39585A (30 micrograms/kg sc). An alpha 2-adrenergic agonist can be used to model gastroparesis in dogs by inhibiting antroduodenal motility and can also be used to examine the actions of motor stimulants, such as renzapride, which promote gastric emptying.
Gastrointestinal Diseases Research Department, G.D. Searle and Co., Skokie, IL 60077.
G W
GW
Gullikson
M A
MA
Virina
R
R
Loeffler
W D
WD
Erwin
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003408:Cresols / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D004386:Duodenum / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D004435:Eating; D005746:Gastric Emptying / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D010243:Paralysis / Q000503:physiopathology*; D011758:Pyrroles / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists; D013272:Stomach Diseases / Q000503:physiopathology*; D013671:Technetium Tc 99m Sulfur Colloid
D000316:Adrenergic alpha-Agonists; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003408:Cresols; D011758:Pyrroles; D011942:Receptors, Adrenergic, alpha; D012702:Serotonin Antagonists; C070769:SC 39585A; D013671:Technetium Tc 99m Sulfur Colloid; C053006:renzapride