Antagonism of KW-5338 (domperidone) against emesis and depression of intestinal motility induced by L-DOPA.
KW-5338 (domperidone), a new dopamine antagonist, is considered to be an agent to cross the blood-brain barrier with difficulty. The antagonistic activities of KW-5338 against L-DOPA were investigated, KW-5338 showed a strong anti-emetic action against L-DOPA induced emesis in beagle dogs (ED50=0.056 mg/kg (p.o.)) and restored the L-DOPA induced depression of intestinal motility to some extent, while it did not antagonize anti-tremorine activities of L-DOPA and trihexyphenidyl in mice. These results suggest that KW-5338 prevents side effects of L-DOPA such as nausea, vomiting and constipation, without reduction in therapeutic effects of L-DOPA in Parkinson's disease.
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D004285:Dogs; D004294:Domperidone / Q000494:pharmacology*; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007980:Levodopa / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D014203:Tremorine / Q000037:antagonists & inhibitors; D014282:Trihexyphenidyl / Q000494:pharmacology
D000932:Antiemetics; D007980:Levodopa; D004294:Domperidone; D014282:Trihexyphenidyl; D014203:Tremorine