抗コリン・エステラーゼ剤—特にパラチオン中毒についての観察と重症筋無力症における抗コリンエステラーゼ剤の応用

　いとぐち　現在吾々が抗コリン・エステラーゼ（Anti-ChE）として持つものは重可成り数多くなつているが大別して2群に分れる。一つは有機燐製剤でDFP，OMPA，TEPP，Parathion等が含まれ，農業薬品として主として用いられ，毒ガスとしての研究も外国においては行われている。コリンエステラーゼ（ChE）と燐酸結合を来たして酵素活性を阻害するが，此の結合は遊離し難く，従つて酵素阻害作用は非可逆的と考えて差支えない。他は抗クラーレ物質として古くから研究が進められた群で，4級アミン化合物を出発点として最近までに幾つかのものが実用に供せられている。此の群には古くから用いられるPhysostigmine，Prostigmineの外，最近はMestinon，Ambenonium，Tensilon，BC₄₀等がつくられ，後の治療的応用においてふれるように臨床的に用いられている。これらはAchについて模型的に示されるようにChEのAnionic site，Esteratic siteのいずれか，或いは両方に結合して酵素作用の阻害を来たす。Ach及びその類似化合物について見られるようにN-Aefher O Distanzが5Å，N-Carbamyl ODistanzが7Åである場合に薬理的作用が最も著しいことは此の群でも同じであり，且又Anti-ChE作用の外にそれ自体Ach様作用を有する。

　It is generally recognized that Anti-ChE compounds have 3 applications.

　In the first place, they are important agents inthe physiological and biochemical studies of Achin the laboratory.

　Secondly, in the treatment of gastrointestinalatonia, glucoma and myasthenia gravis, they arewidely used.

　Thirdly, the organophosphor is used as an insecticides and was-gas. Such an application hasan important problem for physicians because ofaccidental intoxications. Recently the studies oforganophosphor developed to the discovery of Anti-anti-ChE.

　In this paper the second and third problems-parathion intoxication and clinical treatment ofmyasthenia gravis-have been described.

　1. The symptoms and signs of the parathionintoxicated animals are well explained only by its Anti-ChE activity, although paranitrophenol, derived from parathion, is found in certain conceutration in many tissues of the animals.

　The E. E. G. changes, seen in the intoxicatedmonkey, are recovered promptly after the intravenous administration of Anti-anti-ChE-PAM, inin accordance with the recovery of serum, redblood cell and brain ChE activity.

　Probably the parathion dose not affect the SH-enzyme other than ChE, because there is nochange in the succinic dehydrogenase activity ofbrains of the intoxicated animals.

　The remakable histological changes seen in theCNS of the subacutely intoxicated animals resemble these of acute circulatory disturbance. Butthe degree and distribution of damage of nervecells is most severe in the basal ganglia, and thedegree of nerve cell damage is as following order:Pons and medulla oblongata, cerebral cortex, cerebellum. In cerebral cortex the nerve cells indeep layer are more affected than those of superiorlayer. The nerve cell damage is scarcely seenin the cerebellum. This pattern of distribution ofaffected nerve cells resembles with that of ChEactivity in the C. N. S. There are many focusesof "Perivasular Ausfall" of nerve cells, which suggests that the toxic agents affects directly fromthe blood stream. From these observations theauthor concluded that the disturbance of centralnervous function was the result of direct affectionof parathion as an Anti-ChE, and the effect ofacute circulatory insufficiency was insignificant,

　2. At present, mestinon and ambenonium iswidely used for the treatment of myasthenia gravis.The therapeutic effect of mestinon and ambenoniumis not parallel with the inhibition of serum ChEactivity. This phenomen is due to the characteristics of these compounds, that they have not onlyAnti-ChE properties but Anti-Curare activity. Organophosphor (lose not have this anti-Curareactivity, and therefore is not so suitable for thetreatment of myasthenia gravis. Because of moreprolonged effects of anbenonium than prustigmineand mestinon, it is more suitable for clinical use. The serum ChE inhibiting action is less remarkable than the red blood cell ChE inhibiting action. Moreover, ambenonium has another convieniencefor clinical use,-the stimulating action of bronchial secretion of ambenonium is least among Anti-ChE compounds.

　We found that the potasium content of musclewas increased in myasthenics, despite of normalcontent of CTN, CTN-P., and the potassium content decreased to normal level after the administration of Anti-ChE. I believe that this is aninteresting finding in the study of mechanism ofmyasthenia gravis.