実験的錐体外路症候群に関する研究 薬物により惹起されたParkinsonismusネズミの臨床ならびに基底核領域ChE活性の選択的阻害について

1) In order to study the experimental Parkinsonism, some Phenothiazine-Derivatives, e. g. Chlorpromazine 30 mg/Kg., Perphenazine 15 mg/Kg.. Trifluoperazine 5 mg/Kg.. Fulphenazine 5 mg/Kg.. Thioproperazine 10 mg/Kg.; and Bulbocapnine 15 mg/Kg. which had been used for study of the experimental catatonia customally, were injected into the peritoneum of the Cb-strain of male mice and the Wister-strain of male rats. Above 90% of the rats and mice showed parkinsonism after the abministration of these drugs. 2) The parkinsonian rats and mice showed sluggish movements, abnormal postures, catalepsia-like-syndroms e. g. passivity, negativism, fixation, rigidity of muscles, vegetative signs and tremor. Rigidity of muscles was objectively proved by application of the priciple of the Wartenberg's fixation of position test which was adopted to identify parkinsonism clinically and the principle of the Richter's grasp reflex and by appearence of the normal motor units at a strech reflex of the M. Gastrocunemius in the electromyography. 3) As the preliminary experiment, three methods to assay the activity of ChE were each compared using brain homogenates. These were the manometric assay by Ammon's method, the electrometric assay using "glass electrode" PH-meter by the modified Michel's method and the spectrophotometric assay by the modified Takahashi Shibata's method. Among these assay, the electrometric assay was the most accurate method to detect the activity of ChE of the brain. Following studies were carried out using this electrometric assay. 4) The ChE activity of the whole cerebrum of parkinsonian mice induced medicamentally was measured and compared with that of normals using the electrometric assay. All of the Phenothiazine-Derivatives inhibited the ChE activity of the whole cerebrum. But Bulbocapnine did not. 5) The brain of the parkinsonian Wister strain of male rats was separated into two parts. One included the cortical area, the another included the basal ganglia. The ChE activity of both parts was measured by the electrometric assay. In the parkinsonian rats induced by Phenothiazine-Derivatives, the ChE activity of the cortical area was within normal limits but that of the basal gangliar area was remarkably inhibited. Bulbocapnine exaggerated the ChE activity in the cortical parts, while contrastedly inhibited the ChE activity in the basal ganglia. 6) Referring to the correlation of the inhibitory effect and the structures of the Phenothiazine-Derivatives, -CF(3) base which was replaced with 3'-H on the phenothiazine nucleus, had a relatively higher inhibitory effect than the another. Piperazinyl base which attached to the side chain of the Phenothiazine nucleus, had also relatively higher imhibitory effects. 7) The problems occured here were discussed. Especially the correlation between parkinsonism and the possible roles of the cholinergic system, regarding to the change of the behavior of animals and the inhibition of the ChE activity or the basal ganglia of the parkinsonian rats were discussed.