The effects of S(-) and R(+) sulpiride, metoclopramide, cisapride and domperidone on the small intestine suggest DA2-receptors are involved in the control of small intestinal transit time in rats.
To study the effect of intraperitoneal S(-)sulpiride (1-15 mg/kg), R(+)sulpiride (5-10 mg/kg), metoclopramide (1-15 mg/kg), cisapride (10 mg/kg) and domperidone (5-10 mg/kg) on intestinal progression, rats were given the test drug followed by oral lactulose. Their hydrogen excretion was used to calculate the small bowel transit time (SBTT) and maximum peak time (MPT). Metoclopramide (7.5 mg/kg) had the greatest effect on SBTT (-25%), followed by S(-)sulpiride and domperidone. S(-)sulpiride (10 mg/kg) had the greatest activity on the MPT (-35.2%) followed by metoclopramide. R(+)sulpiride and cisapride did not modify SBTT and MPT. In conclusion S(-)sulpiride is the isomer active on intestinal transit and DA2-receptors seem important targets in the modulation of intestinal progression, since S(-)sulpiride, metoclopramide and domperidone are DA2-receptor antagonists, and R(+)sulpiride and cisapride are not. The H2 breath test proved a valid method for measuring the effect of drugs on the small intestine in animals.
Zuccato
E
E
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Bertolo
C
C
Salomoni
M
M
Forgione
A
A
Mussini
E
E
D000818:Animals; D020117:Cisapride; D004294:Domperidone / Q000494:pharmacology; D005772:Gastrointestinal Transit / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013237:Stereoisomerism; D013469:Sulpiride / Q000494:pharmacology
D010880:Piperidines; D017448:Receptors, Dopamine D2; D012702:Serotonin Antagonists; D004294:Domperidone; D013469:Sulpiride; D008787:Metoclopramide; D020117:Cisapride