Shuto K, Shiozaki Z, Kojima T, Tanaka M
J Pharmacobiodyn. 1980 Dec;3(12):709-14. doi: 10.1248/bpb1978.3.709.
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.
新型多巴胺拮抗剂KW-5338（多潘立酮）被认为是一种难以穿越血脑屏障的药物。对KW-5338拮抗左旋多巴的活性进行了研究，KW-5338对比格犬中左旋多巴诱发的呕吐表现出强烈的止吐作用（口服半数有效量=0.056毫克/千克），并在一定程度上恢复了左旋多巴引起的肠道动力抑制，而它并不拮抗左旋多巴和苯海索对小鼠的抗震颤活性。这些结果表明，KW-5338可预防左旋多巴的副作用，如恶心、呕吐和便秘，同时不会降低左旋多巴在帕金森病中的治疗效果。
