Yoshimi Misu (1), Yoshio Goshima (1), Takeaki Miyamae (1), Nobuya Furukawa
(1), Yoshinobu Sugiyama (1), Yoko Okumura (1), Minako Shimizu (1), Etsuo
Ohshima (2) and Fumio Suzuki (2)
(1) Department of Pharmacology, Yokohama City University School of Medicine, Yokohama 236, Japan
(2) Drug Discovery Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Shizuoka 411, Japan
Abstract: We explore stable potent competitive antagonists against L-DOPA. In anesthetized rats, DOPA cyclohexyl ester (DOPA CHE) (30 - 100 ng) microinjected in depressor sites of the nucleus tractus solitarii dose-dependently shifted the dose-response-curve for L-DOPA (18 - 300 ng) to the right, with DOPA CHE (100 ng)-induced slight reduction of the maximum response. DOPA methyl ester (DOPA ME) at 100 ng also produced competitive antagonism. Antagonistic activity of DOPA CHE (100 ng) was similar to that of DOPA ME (300 ng). DOPA CHE is suitable for the purpose of screening.
Keywords: Competitive L-DOPA antagonist, DOPA cyclohexyl ester, Microinjection into the nucleus tractus solitarii