As part of a series, a study concerning the mechanism of the antiparasitic action of 4-iodothymol (IT) on Ascaris body and distribution in the various tissues after absorption was made. It was found to be taken up through the mouth and skin, however the percentage through the skin was greater. In 5hr, 50% was taken up at the concentration of 200μg/ml and almost all was unchanged in Ascaris. The rate of ¹³¹I-IT uptake was greatest in the head, with muscles of the central body being next. A rather small amount was distributed in the perienteric fluid, the gastro-intestinal ducts and the genital organs.

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The authors studied, in two experimental periods (spring and summer), the influence of adrenalectomy or chronic administrations of ACTH on methamphetamine-induced stereotyped behavior (sniffing, biting and licking) and increase of brain amphetamine level in rats. In both spring and summer, the brain amphetamine levels were markedly increased in adrenalectomized rats. Within the limits of the spring experiment, the biting hehavior was not observed in rats which had been treated with ACTH, while the frequent appearance of sniffing behavior in adrenalectomized rats was inhibited by ACTH. Within the limits of the summer experiment, the licking behavior was not seen in rats treated with ACTH, while the lack of biting in adrenalectomized rats was restored with administration of the drug.

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Substrate specificities of Ficin A, B, C and D from Ficus carica var. HORAISHI were examined with bradykinin, dansylbradykinin and synthetic substrates. These enzymes showed kininase activity, but differed greatly in their specific activities. Kinins were not released from bovine plasma kininogen. These enzymes hydrolyzed dansylbradykinin at the site of Gly⁴-Phe⁵ and Phe⁵-Ser⁶, however, the processes of the hydrolysis differed among the enzymes. Toward synthetic substrates, a part of α-N-substituted dipeptides and tripeptide was hydrolyzed but dipeptides were not. From these results, it is suggested that Ficin A, B, C and D show kininase activity, have the same specificity toward dansylbradykinin, and similar specificity toward synthetic substrates.

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Studies on the absorption, tissue distribution, metabolism and excretion of Mendon (¹⁴C (5)-labeled) were carried out. Results are as follows: The blood level reached the highest within approx. 1hr after oral administration, with a rapid decline thereafter, and only a trace was observed after a lapse of 21hr. One hr after oral administration, peak tissue levels of ¹⁴C were observed in both mice and rats. The levels were higher in the liver and kidneys, but the level in the brain was almost as low as that in the blood. In a rabbit, oxazepam and its conjugated form were found mostly in the urine as one of the metabolites of Mendon. The non-changed compound (Mendon), nordiazepam, its conjugated form plus a few unknown compounds were however, also observed. In rats, excretion generally took place within the intestinal tract, while in rabbits, it was through the urinary tract.

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The relationship between pyrogenicity and rat liver mitochondrial functions induced by pyrogenic substances has been investigated herein (E. coli pyrogen, DNP and catecholamines). The following results were obtained. E. coli pyrogen, DNP and N-epinephrine elevated rat rectal temp. following i.p. injection. Mitochondrial respiration was stimulated slightly with the in vitro addition of catecholamine. Oxidative phosphorylation of rat liver mitochondria was decreased after injection of pyrogens but it was reversed with the addition of the supernatant of normal rat liver mitochondria. Mitochondrial ATPase activity was decreased after injection of pyrogen, DNP and catecholamine in rats.

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K-315 in an effective analgesic dose did not vary monoamine levels (nor-adrenaline, dopamine and 5-hydroxytryptamine) in mouse brain. The analgesic action of K-315 was potentiated by cocaine, but not modified by tetrabenazine and p-chlorophenylalanine, though lowered by reserpine and α-methyltyrosine. K-315 was not included in the same category as the other 4 analgesics (morphine, pethidine, dihydrocodeine and aminopyrine), regarding modification of analgesic effects due to variation of monoamine contents in the brain.

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K-315 produces potentiation of catechlamine (CA) actions in vivo and in vitro. The potentiating effect of K-315 is not affected by denervation, decentralization or reserpinization. K-315 inhibits neither MAO nor COMT activities. K-315 depresses the uptake of CA into rabbit blood platelets and mouse brain slices. Mechanisms of CA potentiating effects regarding K-315 are discussed.

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The present report describes the effects of cold storage (1_??_7 days) on the mechanical response of isolated guinea-pig gallbladder to transmural and chemical stimulation. Results obtained are as follows: in the cumulative dose-response analysis, the maximal contractile response to exogenous ACh was gradually reduced during the 1 to 7-day cold storage, however it was not abolished. The pD₂ and pA₂ (of atropine) values were not significantly different between on fresh and cold-stored preparations. The monophasic contraction induced by transmural stimulation was reduced more rapidly during the 1 to 4-day storage and abolished during the 4 to 7-day cold storage. Tetrodotoxin (TTX) or atropine prevented the contractile response to transmural stimulation. On the other hand, atropine, but not TTX, blocked the exogenous ACh-induced contraction. The maximal contractions induced by KCl and by BaCl₂ were gradually reduced during the 1 to 7-day cold storage, while pD₂ and pD₂' (of papaverine) values on cold-stored preparations were not remarkably different from those on fresh preparations. Cold storage reduced the maximal contractile response to phenylephrine, but did not affect the maximal relaxation induced by isoprenaline. The pD₂ and pA₂ (of antagonist) values were not, however, significantly different between fresh and cold-stored preparations. In the K⁺-free medium, ouabain (10^-5M), but not propranolol (3.5×10^-5M) abolished the biphasic response of cold-stored preparations induced by treatment with 5.4mM KCl or by replacement of normal Ringer's solution. These results suggest that the ACh release mechanism of postganglionic cholinergic fibers was blocked after a 4-day storage at 2°C and that the specific receptor level as well as the contractile actomyosin system were unaffected by cold storage up to 7 days. The maximal contractile response was, however, gradually reduced during a one-week period of cold storage. Thus, it appears that the cold storage procedure produces a partial depolarization of cell membrane.

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Rigidity of the decerebrate cat (Sherrington type), as judged from the tonic EMG activity of the extensor muscles, increased moderately with i. v. administration of L-dopa 40mg/kg, as well as an oral administration of 1g/kg. On the other hand, with the same amount of the drug no influence was observed in the anemically decerebrate cat (Pollock-Davis type). In the anesthetized spinal cat, lumbar mono- and poly-synaptic reflex activities, as well as the dorsal root reflex activity, were not influenced by 1g/kg of L-dopa given orally. In the pentobarbitalized intact cat the spontaneous spindle activity recorded from the lumbar dorsal roots, was depressed slightly, after oral administration of 1g/kg of L-dopa. The effect was not seen until one hour after ingestion of the drug. Facilitatory effects of the muscle spindle afferent, induced by high frequency stimulation of the supraspinal structures, such as the cerebral cortex, caudate nucleus, mesencephalic reticular formation, as seen in the discharge rates of single GIa spindle afferent activity of ankle flexors and extensor were depressed by oral administration of 1g/kg L-dopa. Further, in the ankle extensor GIa afferents, facilitation from the cerebellum was slightly depressed while that from the posterior region of the hypothalamus was not when the same dose of L-dopa was given. As for the flexor GIa afferents, thereshold values for inducing the facilitation from the motor cortex, caudate and reticular formation also increased 20, 30, and 250%, respectively with oral L-dopa administration. In these tests, direct effects of the drug on muscle spindle were not found. A significant blood pressure increase was observed with i. v. administration of 60mg/kg, but with oral L-dopa, 1g/kg, only a slight increase was seen in 1 out of 5 cats. With a dose of 0.5g/kg no change was seen in the blood pressure but the difference between the systolic and diastolic pressures were quite significant. The respiration rate increased moderately with i. v. as well as oral administrations. Possible mechanisms of L-dopa actions were discussed.

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Tibial nerve of adult cats was cut at the level of the popliteal fossa and the epineurium of the cut ends was sutured immediately after the cutting with the aid of special rings. Vitamin B₁, B₆ and B₁₂ complex (B₁, 5mg/kg, B₆, 5mg/kg and B₁₂, 50γ/kg) were injected i. m. daily for about 80 days, and the effects on nerve regeneration were investigated and compared with components. Greater effects of vitamin B₁, B₆ and B₁₂ complex than those of its components were as follows. 1) Gastrocnemius muscle tension. 2) Gastrocnemius muscle wt. ratio. 3) Nerve connection of the gastrocnemius muscle spindles and Golgi tendon organs. 4) Decubital ulcer and depilation (greater in decubital ulcer). In the soleus muscle tension and wt. ratio, no such superior effects were observed. The components of vitamin B complex (B₁, B₆ and B₁₂) did not differ significantly in muscle tension, muscle wt. ratio, decubital ulcer and depilation.

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