Serum β-glucuronidase activity has been found to be increased in various diseases of human subjects as well as in experimental animals. Recently, it was reported by Goldbarg et al. (1), Dohrmann (2, 3) and Hagenfeldt and Wahlberg (4) that serum β-glucuronidase activity in diabetic patients was higher than that of normal subjects, though any definite relationship between the enzyme activity and blood sugar level or urinary excretion of glucose was not observed. We also obtained similar results (5) in the experiments which were designed to investigate the relationship between serum β-glucuronidase activity and the conditions in experimental diabetic rabbits.
In the course of our study, it was found that the administration of glucose to the rabbit caused an increase in serum β-glucuronidase activity, while the injection of insulin produced a decrease in the enzyme activity, and furthermore, these changes in the enzyme activity appeared to be parallel to blood sugar level.
The increasing interest in any possible significance of the β-glucuronidase activity changes has developed, although these phenomena has not been elucidated yet. The experiments described in this paper deal with the effects of hypo- or hyperglycemia caused by the administration of glucose or some hormones on serum β-glucuronidase activity in rabbit.

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It is a well known phenomenon that brief heating of the crude extract of pituitary gland in dilute alkali-solution potentiates its melanocyte-darkening activity and prolongs the duration of its action. This phenomenon has been investigated by two groups of investigators (1-4) using homogeneous MSHs and ACTH with which MSH activity of pituitary extract is shared. It was found that heating in alkali invariably induced racemization of the constituent amino acids of these hormones and the modified actions of alkali-treated hormones were explained in terms of their racemized structures.
Yajima et al. have recently accomplished the synthesis of nine stereoisomers of L-histidyl-L-phenylalanyl-L-arginyl-L-tryptophyl-glycine (all-L) which was suggested by Hofmann et al. (5) as the active site of these hormones.
In this paper, details of our in vitro assay method using Rana nigromaculata H. and the activities of the nine stereoisomers estimated by this method will be given. A certain part of this experiment has already been appeared (6).

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Hafliger (1) synthesized a series of iminodibenzyl compounds which were found to possess antihistaminic, anticholinergic, sedative and analgesic properties. It was only after a clinical trial by Kuhn (2) that G 22355 (imipramine) “emerged as an antidepressant”. The exact mechanism of the antidepressant action of imipramine (IMI), its derivative desmethylimipramine (DMI) and its analogue amitriptyline (AMI) is not yet established. These agents have been shown to antagonise reserpine induced muscular rigidity and this effect has been attributed to their central cholinolytic activity (3, 4). Another structurally related antidepressant, orphenadrine, has been reported to possess both central (5) and peripheral (6) muscle relaxant properties. We have, earlier, reported the inhibition of myoneural transmissson by IMI, DMI and AMI (7). Prolonged inhibition of linguomandibular reflex by low doses of these agents as compared to short lived action of mephenesin (8) prompted us to find out if these agents fulfill all the criteria essential for a central muscle relaxant. Accordingly, these drugs were subjected to various test procedures like effect on behaviour, effect on polysynaptic linguomandibular reflex, effect on facilitatory influence of reticular formation on patellar reflex and the effect on decerebrate muscular rigidity in cat.

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A number of reports (1) have been appeared in attempt to explain the pathogenesis of essential hypertension from the pathological, pharmacological and epidemiological points of view.
It has recently been demonstrated that norepinephrine (NE) and serotonin (5HT) are important transmitters of the nervous system. In addition, metabolic pathway of these amines has recently been clarified (2-4).
The present study is primarily concerned with a comparison between normotensive Wistar strain rats and spontaneously hypertensive rats separated from the same strain through the selective inbreedings by Okamoto and his colaborators (5). They mated Wistar strain rats which showed slightly higher blood pressure than the average under normal conditions. Continuously hypertensive first generation rats were selected and mated again in brother-sister breedings, until by serial reperation of this method, a spontaneously hypertensive colony of Wistar rats was obtained.
This hypertensive colony is useful for these experiments, because it is not so difficult to obtain numerous offsprings and they keep an average span of life, and it is not necessary to turn to any particular agent like DOCA or surgical operation to obtain hypertension. They show an almost 100% occurrence of over 150 mmHg of blood pressure after 25 weeks of age. Pathological changes (6) such as heart hypertrophy, thickening of blood vessels, and nephrosclerosis after the maintenance of hypertension being satisfactory for experimental hypertension, and it may be comparable with human essential hypertension.
The purpose of this study is to ascertain whether the metabolism of monoamines is consistently associated with hypertension or not, by means of comparison, on 5HT and NE metabolism has been made between normotensive and hypertensive rats.

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The present authors (1-3) have reported that the evoked potentials and ensuing rhythmic after-discharges in the auditory cortex of the unanesthetized cat caused by click stimuli are easily affected by change of environmental conditions. Furthermore, they have found that pentobarbital sodium, chloralose and chlorpromazine in small doses increase the magnitude of the cortical click responses without facilitating the evoked click responses in the inferior colliculus. Urethane and ethyl alcohol are quite unique in their actions, producing only a progressive decrease in the cortical responses.
Since the demonstration of central role of the reticular formation (RF) in the brain mechanisms by Moruzzi and Magoun (4), the ascending inhibitory and facili tatory functions have been discussed by many investigators. Domino (5) and Killam (6) have emphasized that the potentiation of the recruiting response by barbiturates is due to a release phenomenon of the recovery cycle in the thalamic relay through the ascending influence of the brain stem RE In the previous papers (1, 3), small doses of pento barbital sodium, chloralose and chlorpromazine are likely to facilitate the transmission of the auditory ascending impulses to the auditory cortex by inhibiting the activity of RE The essential role of the RF in modification of the evoked auditory responses has been described by Hernandez-Peon et al. (7, 8), Desmedt et al. (9) and Chin et al. (10). However, the complex nature of interaction between the auditory responses and the RF still remains to be settled in detail.
In the present experiments the effects of electrical stimulation of the RF on the click responses in the auditory cortex and the relay nuclei were studied before and after the administration of central depressants in the cat.

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The role of the hypothalamus in the eating act and the regulation of food intake has recently been established in experimental animals by stimulation and destruction of the structure. The hyperphagia with obesity and the aphagia produced by the hypothalamic lesions indicates the localization of two regulatory centers, mutually antagonistic in function, i.e. the satiety center and the feeding center. The satiety center is presumedly involved in regulation of food intake responding to the changes of visceral sensations or blood concentration of metabolic products. The destruction of the ventromedial hypothalamic region has been shown to produce hyperphagia and obesity in a variety of animals.
Apart from the study on the regulation of food intake, attempts have been made to elucidate other aspects of the eating behavior, that is, the motivation mechanism by observing the hunger-motivated behaviors or the conditioned responses. In hypothalamically hyperphagic rats, Miller et al. (1) have shown that their hunger-motivated behaviors are more easily depressed than in normal ones. In the experiments to present the possible involvement of the satiety center in the anorexigenic effect of amphetamine Epstein (2) and Reynolds (3) have found that the reduction of food intake induced by the drug is more marked in hypothalamically hyperphagic rats than in intact ones. From the observation that hypothalamically hyperphagic rats overate the dextrose-added diet, but refused to eat it when cellulose or quinine was added to the food which was still acceptable to normal rats, Teitelbaum (4) regarded them as finicky eaters. Epstein (2) suggested that this notion of finickiness might be extended to all feeding situations in the hypothalamus-lesioned hyperphagic rats.
Some pharmacological agents have been known to reduce or enchance the appetite. One of them is amphetamine, and, with other sympathomimetic drugs, it has been often used clinically in obesity control. Schmidt and Van Meter (5) observed a depressing effect of chlorpromazine on food intake in rats, and chlordiazepoxide was reported to augment the food intake and to accelerate the increase of body weight in rats and dogs (6). The clinical observations with reserpine also suggest some effects on the appetite. In the present experiment, effects of some centrally acting drugs on the hypothalamic regulatory mechanisms of feeding have been examined by observing the eating behaviors in intact and hypothalamus-lesioned rats.

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Haffner's tail-pinch method (1) for testing analgesic drugs has been adopted in many laboratories either in the original method (2-4, 17) or in the varieties of modifications (5-7). Certain objections can, however, be raised against the use of the Haffner's method; the intensity of the painful stimulus produced by this method is not shown in figures, neither is it varied quantitatively.
The improvement of these disadvantages has been carried out by Eddy (8), Friend and Harris (9), Fleish and Dolivo (10), Brodie et al. (11), Green and Young (12), Yanai (13), Takagi and Kameyama (14), and so on, but there seems still no ideal method exists.
The Authors discribe here a simple tail-pinch method, which the intensity of pressure stimulus is varied quantitatively and which satisfies the sensitivity and reproducibility for testing non-narcotic analgesics as well as narcotics.

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Referring to the relationship between the pharmacological actions of nicotine and the biogenic active substances, a certain biogenic amine released by nicotine has been suggested to participate in some pharmacological actions of nicotine (1). Especially the release of epinephrine from the adrenal medulla by nicotine has been proven (2-7). The significance of the actions of biogenic amines has been recognized to elucidate the mechanism of the drug actions, since much more reliable methods of assays for identification were developed (8-13).
The present experiment was designed to observe the relationship between the contents of the biogenic catechols in the several tissues of rats and the behavial changes of three patterns of nicotine-induced convulsions.

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It has been reported that spleen strips contract with an addition of adrenaline (13), noradrenaline (3), acetylcholine (1-3), histamine (1-2) or 5-hydroxytryptamine (2) to the bath medium. The adrenaline-induced contraction of the spleen strips can be blocked by alpha-adrenergic blocking agents (1-4). According to Bickerton (4), isoproterenol, which stimulates beta-adrenergic receptors, also contracts the spleen strips and the isoproterenol-induced contraction is specifically blocked by a beta-adrenergic blocking agent, dichloroisoproterenol (5).
The present paper describes that pronethalol, one of the beta-adrenergic blocking agents originally reported by Black and Stephenson (6), inhibits the contraction of spleen strips produced by adrenaline, acetylcholine or isoproterenol, in different species of animals.

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Bei dem Versuche, festzustellen, ob die Tiere imstande Bind. Vitamin B₁ aus semen beiden Bausteinen, der Thiazol and der Pyrimidinkomponente zu synthetisieren, haben Abderhalden (1) and dann Morii (2) gefunden, dass bei Vitamin B₁-frei ernährten Mäusen, Ratten and Meerschweinchen nach parenteraler Zufuhr von 0.12-0.2 mg 2-Methyl-4-amino-5-hydroxymethylpyrimidin (oder seinem Halogenderivat) plus Thiazolkomponente pro Gramm Körpergewicht schwere Krämpfe auftraten, die innerhalb weniger Stunden zum Tode führten. Es liess sich leicht zeigen, dass die Ursache dieserErscheinung in der Zufuhr der Pyrimidinderivate zu suchen war. Von grossem Interesse ist die Tatsache, dass die beschriebene Wirkung der Pyrimidinkomponente des Aneurins offenbar in spezifischer Weise an ihre Konstitution gebunden ist. Versuche mit anderen Pyrimidinderivaten, Urazil, Thymin, Adenyls¨aure, 2-Methyl-6-amino-5-aminomethylpyrimidin, 2-Amino-4-äthylpyrimidin, 4-Äthyl-6-aminopyrimidin, 2-Äthyl-4-amino-5-bromäthylpyrimidin, 4-Amino-5-chlormethyl-6-methylpyrimidin usw. ergaben nämlich, dass die Zufuhr von grösseren Mengen dieser Verbindungen keinerlei Erscheinugen hervorruft. Auch Abderhalden hat berichtet, dass durch Zufuhr von Gynergen, Cortidyn, Traubenzucker oder Vitamin B₁ die Krämpfe weder verhindert, noch beeinflusst werden konnten. Dagegen gelang es ihm, sic durch Herbeifuhrung eines Evipan bzw. Luminalschlafes zum Verschwinden zu bringen. Makino and andere (3, 4) haben einen Antagonismus zwischen 2Methyl-4-amino-5-hydroxymethylpyrimidin and Vitamin B₆-Gruppe bestätigt, welche die durch Zufuhr von diesem Pyrimidinderivat verursachten Krämpfe verhindern and zum Verschwinden bringen konnte. Seither wurden Forschungsergebnisse auf diesem Gebiet mässig lebhaft verötffentlicht. Vor allem bestätigte Miyake (5), dass auch andere Pyrimidinderivate, 2, 5-Dimethyl-4-aminopyrimidin and 2, 6-Dimethyl-4-aminopyrimidin, zu rennenden Krampfen (“running fit”) der Maus Veranlassung geben. Diesen Gesichtspunkten Rechnung tragend, wurden these Pyrimidinverbindungen gemeinsam als Gruppe von Toxopyrimidin (Abkürzung TXP), besonders 2-Methyl-4-amino-5-hydroxymethylpyrimidin als Oxymethylpyrimidin (Abkürzung OMP) bezeichnet. Muraoka (6) führte als eine andere hemmende Substanz für OMP-Krampfe ausser der Vitamin B₆-Gruppe γ-Amino-β-hydroxybuttersäure an. Auch nach Nagai (7), Yabuuchi and anderen (8) wurde angenommen, dass γ-Amino-β-hydroxybuttersaure ein physiologischer hemmender Stoff für Krämpfe sei. Dagegen konnten Enomoto and andere (9) in hiesigem Institut keine unverkennbare krampfstillende Wirkung dieser ω-Aminosäure bestätigen.
In vorliegenden Versuchen habe ich die hemmende Wirkung der dl-γ-Amino-β-hydroxybuttersäure fur OMP-Krämpfe einer weiteren Prüfung unterzogen. Fernerhin wurde gleichartige Durchsuchung der optisch aktiven Verbindungen dieser ω-Aminosäure, der 1-Amino-2-hydroxypropansulfonsäure and ihrer Derivate usw. in Angriff genommen.

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