Antagonism of KW-5338 (domperidone) against emesis and depression of intestinal motility induced by L-DOPA.

Abstract

KW-5338 (domperidone), a new dopamine antagonist, is an agent which crosses the blood-brain barrier with difficulty. The antagonistic activities of KW-5338 against L-dopa were investigated. KW-5338 showed a strong antiemetic action against L-dopa-induced emesis in beagle dogs (ED50 = 0.056 mg/kg (p.o., per os)) and restored the L-dopa-induced depression of intestinal motility to some extent, while it did not antagonize antitremorine activities of L-dopa and trihexyphenidyl in mice. KW-5338 prevents side effects of L-dopa, i.e., nausea, vomiting and constipation, without reduction in therapeutic effects of L-dopa in Parkinson''s disease.