岡山医学会 Acta Medica Okayama 0030-1558 72 4 1960 Acetanilide及びPyrazolone系二，三誘導体の抗炎症作用とHistamine遊離抑制作用 1091 1096 EN Hidemasa Yamasaki Kazuji Kondo Teruo Uda Three acetanilide and two pyrazolene derivatives were tested for anti-inflammatory effect on the edema of rat's hind-paws induced by the local injection of dextran, hyaluronidase, formaldehyde, histamine and 5-hydroxyptamine, and for histamine-release inhibitory effect on the rat receiving an intraperitoneal injection of ovomucoid which increases urinary output of histamine as a result of histamine release in the whole body. Phenacetin, acetanilide, aminopyrine, aminopropylone and butazolidine served as controls. GP-I, one of the pyrazolone derivatives (for formula cf. table 1), showed fairly marked supression on all 5 kinds of edema with effects comparable to aminopyrine and butazolidine. Acetanilide derivatives tested, also exerted marked inhibition on the edema other than by hyaluronidase or formaldehyde. All the compounds inhibited the histamine release due to ovomucoid injection, but no graded difference could be seen. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 5-2 1959 犬のPeptoneショック及びアナフィラキシー・ショックにおける二次的活性物質の検索 2737 2742 EN Hidemasa Yamasaki Kei Jinzenji Kazuji Kondo In dogs immediately after the shock induced by Witte peptone 300mg/kg or by bovine serum anaphylaxis, the presence of adenine nucleotides or 5-hydroxytryptamine in the blood plasma obtained from the femoral and hepatic veins were examined. But our present methods of spectrophotometry of the deproteinized plasma or paper chromtography of the deproteinized, freeze-dried plasma failed to reveal any increase in either substance of these. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 6-2 1959 ラットにおけるHistamineの尿中排泄に関する研究 第2報 Histamineの尿中排泄に対する諸種Histamine遊離物質及びHistamine遊離に影響を及ぼす物質の作用 3289 3299 EN Kazuji Kondo With the administration of histamine there occurs a transient increase of the urinary excretion of free histamine in the female rat being loaded with water and whose urine being collected every 30 minutes. In the previous paper (Folia pharmacol. japon. 54, 1221, 1958) it was reported that such an increase is dependent upon the basal rate (a) of the urinary excretion of histamine and the amount (b) of histamine excessively excreted after intraperitoneal injection of a limited amount of histamine and that there is a relationship of b/a=k (k stands for constant pertaining dose). On the basis of these findings and taking the increase in the urinary excretion of histamine as an index, the author compared the potency and time course of in vivo histamine release as demonstrated by sinomenine hydrochloride, Compound 48/80, quinine hydrochoride, sodium cholate, dextran, egg white, decylamine and Tween 20, administered intraperitoneally. Judging from the relationship between the degree of the increase in the urinary excretion of histamine and the amount of the substances being administered, the histamine-releasing ability of these substances was found to be in the order of; Compound 48/80>decylamine>sinomenine>sodium cholate>quinine, Tween 20>dextran and egg white. Of them, Compound 48/80 and sinomenine showed the increase in the urinary histamine exactly identical with that observed after histamine administration, taking the shortest time course; while in the cases of quinine, sodium cholate, dextran, and egg white the increase was somewhat slower; and by decylamine and Tween 20 it developed most slowly yet most persistently. In the rats previously treated with guaiazulene, cortisone, aminopyrine or cinchophen sodium, increases in the urinary excretion of histamine by all the releasers mentioned above were similarly inhibited. Since mechanisms of histamine release action are not the same by different releasers, it seems that the action of these inhibitors is of such a nature as to be manifested at a common stage involved in different patterns of the mechanism of histamine release. Such an action of cortisone was more marked in a relatively small dose rather than in a large dose, suggesting presence of an adequate amount of this steroid to be used for the manifestation of this action. The histamine-releasing ability of egg white was inhibited in the alloxan-diabetic rat, while on the contrary, it was greatly accelerated in the insulin-treated rat. Such an effect of alloxan was completely antagonized by an adequate amount of insulin. However, in the rat with glycosuria induced by glucose administration, sensitivity to egg white was not altered. Succinic acid or oxaloacetic acid given with the purpose to inhibit the formation of keton bodies, could not eliminate the above mentioned alloxan effect. Both alloxan and insulin did not in any way modify the histamine-releasing effect of sinomenine. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 10-1 1959 Dimethoxyisoquinoline誘導体についての二，三薬理学的検索 6223 6230 EN Akio Kuroda Kei Jinzenji Takashi Yamamoto Kazuji Kondo Junzo Shoda Twelve members of a new series of 1-trialkylmethyl-1-6, 7-dimethoxy-3, 4-dihydroisoquinoline (D type) and eleven analogs of 1-trialkylmethyl-6, 7-dimethoxy isoquinoline (I type) were investigated for their pharmacological properties, with special reference to the toxicity and spasmolytic activity, comparing with papaverine. Along these isoquinoline, 1-methylisoquinoline, 6, 7-dimethoxyisoquinoline and their respective 3, 4-hydrogenated derivatives, were also examined for the elucidation of structure-activity relationship. All the compounds of D type produced a marked inhibitory action on the isolated rabbit intestine. The most potent members were n-tripropyl, ethyl-n-propyl-n-butyl and methyl-ethyl-n-butyl derivatives. Their spasmolytic actions on both barium and histamine contraction of the intestine exceeded those of papaverine, though the effect on acetylcholine spasm was slightly inferior. They were less toxic in mice than in the latter. The intestine inhibitory activity and toxicity of I Type compounds were both smaller than those of D type analogs. The differences between the two types seemed to be related to the solubility. Other smaller components of the papaverine structure, namely, the primitive isoquinoline derivatives were more toxic, but much less spasmolytic than papaverine. In mice toxic doses of all the compounds caused tremors, excitability and convulsions followed by a generalized central depression. Respiratory paralysis may be direct cause of death. Toxic symptoms were generally similar to those in frogs. The stimulant properties were increased by the saturation of the 3, 4-position on the isoquinoline nucleus. No potential conflict of interest relevant to this article was reported.