The female sex hormones are known to influence the activity of the central nervous system. Estrogens facilitate ovulation by promoting the release of luteinizing hormone from the anterior pituitary through hypothalamic action (1). Both estrone and stilboestrol stimulate the running activity of female as well as male rats (2). Progesterone on the other hand, blocks ovulation by its central action (3) and depresses the central nervous system. Large doses may even induce anaesthesia (4). The mechanisms by which these female sex hormones influence the activity of central nervous system is not known. There is enough evidence to suggest the role of catecholamines in the motor activity and ovulation (5-7). It seems that these hormones may be acting in the central nervous system through the involvement of adrenergic mechanism. We have tried to examine this possibility by studying the changes in brain catecholamine content folowing estrogen (diethyl-stilboestrol) and progesterone administration.

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It is well known that morphine produces hyperglycemia in some laboratory animals such as rats, dogs and so on (1) by inducing the release of catecholamine from the adrenal medulla (2). As catecholamine raises the level of free fatty acids (FFA) in blood as well as that of glucose (3), there would be a possibility that morphine also raises the level of FFA in blood. On the other hand the changes of FFA in serum by the administration of morphine were reported scarcely (4, 5). The purpose of the present investigation was to examine the changes of the level of FFA in serum of the morphine-tolerant and nontolerant rats by the administration of or by the withdrawal from morphine, and was also to see whether the level of FFA in serum of the rats changed in parallel with that of glucose in blood when the rats were treated with morphine.
In some cases, the content of FFA of the epididymal fat pad and the rate of lipolysis were examined in order to know the effect of morphine on the lipolysis of the adipose tissue, which is supposed to change the level of FFA in serum.

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The salivary glands, which are innervated by both sympathetic and parasympathetic nervous systems, receive their main secretory innervation from the parasympathetic nervous system (1). It was reported that sympathetic nervous system played an important role in secretion of amylase, a main component of parotid saliva, and that the β receptors were the ones involved in this mechanism (2-5). It was also reported that nicotine caused an increase in amylase secretion as well as salivary flow and suggested that the increasing effect of nicotine on amylase secretion was not due to the direct action on the ganglion, but the action of catecholamine released from adrenal medulla. The acceleration of nicotine in salivary flow, however, was not explained in the same way (6, 7). On the other hand, it was proposed in various organs that symapthetic effect of tyramine was caused by a release of noradrenaline from sympathetic nerve endings (8). It is, therefore, of interest to examine actions of tyramine on amylase secretion in comparison with those of nicotine.

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It is generally accepted that urine is concentrated by the mammalian kidney through the operation of a countercurrent mechanism in the renal medulla and that active sodium transport out of the ascending limb of Henle's loop plays an important role in this mechanism. In addition, it has been reported that in the adrenalectomized rat urine volume is decreased and the corticomedullary osmotic gradient lowered (1, 2).
Experiments studying the effects of aldosterone on free water clearance (3) and the attainment of maximum urinary osmolality (4), have suggested that aldosterone may cause an increased rate of transport of sodium from the inside of the ascending limb of Henle's loop to the surrounding tissue. On the other hand, the action of glucocorticoids, particularly their effects on the loop of Henle have not yet been precisely defined. Experiments dealing with free water reabsorption (T^cH₂O) indicated, that glucocorticoids may enhance sodium transport at the ascending limb (5, 6). Hierholzer's experiments (7) suggested that cortisol affects the water permeability of distal tubular segments. In the present experiments we have attempted, by microperfusion of Henle's loop in the kidneys of adrenalectomized rats, to clarify the mode of action of corticosteroids on these tubular segments.

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Although the blood histamine concentration during normal pregnancy is within the normal range, the serum histaminolytic power is greatly increased (1-3). This remarkable increase in serum histaminolytic power is much more characteristic of pregnancy in man than in any other animals (4). The increase in serum histaminase activity starts as a rule during the second or third month, reaching a maximum in the fifth to the seventh month at which level it remains with modest variations until full term. It then rapidly returns within 3 or 4 days postpartum to the negligible values as found in normal nonpregnant women (2).
The placenta is very rich in histaminase activity (5) and is the principal source of increased serum enzyme activity (6). Pathological changes in the placenta can, therefore, be expected to produce alterations in the normal pattern or sequence of changes in the serum histaminolytic power during pregnancy.
Lindberg (6) recently showed that an intravenous infusion of histamine resulted in a lower concentration of histamine in blood when a woman was pregnant, and that administration of aminoguanidine, an inhibitor of histaminase, to pregnant women raised the concentration of histamine in blood (7).
It has been suggested that deviations from the normal pattern of increase in serum histaminase activity are indicative of an abnormal pregnancy (1), and variable changes in the enzyme activity in cases of pre-eclampsia have been reported (8). Studies on urinary excretion of histamine in cases of pre-eclampsia (9) suggest that there is increased concentration of histamine in circulation under this condition.
Until recently, it has been thought that serum histaminase estimations might possibly serve to indicate indirectly the histamine content of blood, and that the high histaminolytic power of blood could thus be satisfactorily correlated with the common clinical observation of remission of allergic manifestations during pregnancy. Hopes were entertained of throwing light on the significance of tissue and blood histamine via studies of this factor, in the same way that studies of acetylcholinesterase have yielded valuable information on the functions of acetylcholine in the body. The reported similarities between lesions produced by experimental poisoning with histamine in pregnant animals and the clinico-pathological features of pre-eclampsia and eclampsia, and the partly difect and partly indirect evidences that have accumulated pointing toward an excess of circulating histamine in pre-eclampsia and eclampsia together with the establishment of the fact that histamine produces definite hypertensive effects under certain conditions have stimulated our interest in the study of the problem of histamine metabolism in normal and toxaemic pregnancy, and have led to the hypothesis that histamine plays a decisive role in the aetiology of preeclampsia and eclampsia, which has, hitherto, eluded discovery despite extensive research in the past six decades.
It seemed desirable from the foregone facts to investigate into the possible variations from normal of the serum histaminase and whole blood histamine contents in pre-eclampsia and eclampsia, and also to make an attempt to find out the correlation, if any, between the enzyme activity and blood histarnine concentration and the severity of the condition.

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Chlorpromazine has been reported to suppress cardiac arrhythrnias produced experimentally (1, 2) and those observed in clinical practice (3). Two new phenothiazine derivatives, namely piperacetazine (2-acetyl-10-{-3 [-4-(β-hydroxyethyl)-piperidine] propyl}-phenothiazine) and benzosulfonate (1-methyl-2-{-(2-methylsulfinyl-dibenzothiazinyl-10)-ethyl-1 }-piperidine) have been recently synthesized (4, 5). Hence it is of interest to determine if they possess antiarrhythmic activity.

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Since the introduction of dibenzepine (Noveril®) in the medical practice, this compound has been used for the management of depression. Stille et al. (1) have suggested that dibenzepine should be placed somewhere between imipramine and desipramine. In our laboratory we were engaged in an investigation on the influence of substitution on the tricyclic group on the biological activities of this type of compounds and found that the new compound, 5-methyl-8-ethylsulfonyl-10-(2-dimethylaminoethyl)-5H-dibenzo [b, e] [1, 4] diazepine-11 (10)-one (SM-307) was as potent as dibenzepine with regard to antagonism of reserpine induced hypothermia and had lower toxicity than dibenzepine. The present report serves to confirm some of the antidepressive effects of SM-307 compared with imipramine and other antidepressive substances.

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In a previous paper (1) to clarify the physiological significance of endogenous 5-hydroxytryptamine (5-HT) the subcellular distribution of 5-HT in rabbit brain stem has been studied and the electron microscopical structures of the fractions which contain 5-HT have been examined. 5-HT was principally found in P₂-fraction which consisted largely of mitochondria and nerve-ending particles (NEPs). After density-gradient centrifugation 5-HT was found to be comparatively highly concentrated in NEPs-fraction (P₂B-fraction). On the other hand suspension of P₂-fraction in hypo-osmotic medium and subsequent differential centrifugation resulted in high concentration of 5-HT in synaptic vesicles (sv) fraction although considerable amount of 5-HT was also found in P₂D- and P₂S-fraction. In general 5-HT in brain stem was not so highly concentrated in specific fraction as with the distribution of acetylcholine (ACh) (2, 3) but rather diffusibly distributed among several fractions.
In this paper the role of 5-HT in synaptic transmission, especially in central nervous system was investigated mainly through the experiments on 5-HT uptake by subcellular fraction of rabbit brain stem. The chemical transmission at synapses consists of the following consecutive steps: 1) release of transmitter by synaptic impulses. 2) combination of transmitter with postsynaptic receptor. 3) generation of impulses by postsynaptic potential. It appears that the study into the formation, uptake, storage, release and inactivation of 5-HT is necessary for full and accurate understanding of mechanism of chemical transmission, especially when there is no direct evidence for that 5-HT is synaptic transmitter in central nervous system. Segawa and Kuruma (4), Segawa et al. (5) in this laboratory have already shown that NEPs or sv of brain, when incubated in a medium containing 5-HT, could take up 5-HT from the medium and some drugs could inhibit the uptake of 5-HT. However we have as yet very little information as to whether NEPs or sv are specific uptake and storage site for 5-HT in situ. Also the mechanisms with which amine can be taken up by synapses and drug inhibits the uptake are poorly understood. The following is a systematic study concerning the mechanism of 5-HT uptake and drug effect.

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Bendazac or 1-benzyl-indazole 3-oxyacetic acid is a topical antinflammatory drug which in previous experiments was shown to preferentially inhibit inflammatory processes progressing towards necrosis (1). This activity has been temptatively related to a prevention of protein denaturation (2-4).
The aim of these experiments was to study effects of bendazac and hydrocortisone on heat-induced burns and on acetic acid-induced erythema. Two differently formulated creams have been investigated, in an attempt to find out the most suitable one for topical uses.

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Micropuncture studies of the tubules accesible on the surface of the mammalian kidney have been performed usually in the rat, dog and monkey. The tubular fluid from early distal tubule in the rat was always hypotonic to plasma (1), but it reached isotonic to plasma in the late portion of the distal tubule (2-5). In contrast to the observation in the rat, it has been demonstrated that the tubular fluid was markedly hypotonic to plasma along the entire length of the distal tubule in the dog during antidiuretic as well as diuretic state (6, 7). In the kidney of the rhesus monkey, the distal tubular fluid was also hypotonic to plasma during hydropenia (8). The fact mentioned above has suggested that the distal tubular function of the rat kidney was different from that of the dog and monkey kidney. The micropuncture study of the cat kidney has not been reported.
The present study was designed to investigate the pattern of the tubular function of the cat kidney.

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Bradykinin (BK) is widely regarded as a potent vasodilator capable of increasing blood flow, increasing vascular permeability, and lowering systemic blood pressure through microcirculatory dilatation.
On the other hand, reports have appeared in the literature which indicate that BK may constrict some vessels. Lecomte and Trouquet (1), Gersmyer and Spitzbarth (2) and Klupp and Konzett (3) demonstrated the constriction of the lung vessel. Guth et al. (4) and Rowley (5) reported that BK caused venoconstriction of the rabbit ear and rat skin, respectively. Shimamoto et al. (6) also reported the constriction of the rabbit saphenous vein by BK.
The present experiments were undertaken to clarify the BK action on the various portions of blood vessel using several methods. Furthermore some tests were tried to study on the mechanism of venoconstrictive action of BK.

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Mitchell, Dodge (1) and Day (2) reported that cataract develops in rats fed on hyperlactose and hypergalactose diets. Consequently, lactose and galactose are regarded as factors in cataract development. On the other hand, Takuma and Takayama (3) observed that cataracts developed from purified lactose can be inhibited by the addition of whey to the diet. Similar results were obtained by Tamura and coworkers (4). However, the nature of the factor in whey playing a key role here has not been determined. In 1957, Ogihara (5), one of our laboratory staff, reported that neutral fatty acids in whey have this inhibiting effect. Later, we made studies of the factor contained in whey and whey powder and further advanced the analytical studies of these fatty acids.

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It has been long recognized that severe diarrhea, sometimes followed by death, develops in young albino rats and mice because of hyperlactose and hypergalactose diets and that rat cataract also develops. Similar results have been reported by Guha (1). It was described in our previous paper (2, 3) that symptoms resulted from the activity of Leloir's enzyme system being deranged by the excessive lactose and galactose.
On the other hand, Takuma, Takayama (4) Tamura, and their co-workers (5) confirmed the fact that preventive factors inhibiting death due to diarrhea and cataract are contained in whey. It has also been demonstrated in a previous paper that the factors preventing cataract developed in rats fed on a hyperlactose diet were lower neutral saturated fatty acid. However, the factors to prevent death due to diarrhea and nutritional disorder seem to be different from those to inhibit cataract. Accordingly, we conducted studies on this point.

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It has been reported that benzodioxan derivatives, e.q. 2-alkoxymethyl 1.4-benzodioxan (1) and 2-(3'-methoxypropylaminomethyl) 1.4-benzodioxan (Quiloflex) (2, 3) have adrenergic α-blocking, sedative and spinal reflex depressing properties.
Through our intensive pharmacological screening of benzofuran derivatives which possess quite similar chemical structure with 1.4-benzodioxan ring, we found that most of these compounds revealed the similar pharmacological properties to the benzodioxan derivatives (4). It is very interesting that 2-(3'-alkoxypropylaminomethyl) 2.3-dihydrobenzofuran analogues which showed relatively potent skeletal muscle relaxant, sedative, analgesic and adrenergic α-blocking actions, were very similar to chemical structure of Quiloflex.
The purpose of our present work was to investigate the structure-activity relationships of 5 or 7 substituted 2-(3'-alkoxypropylaminomethyl) 2.3-dihydrobenzofuran analogues, particulary of the substituents and their position on the ring concerning analgesic, spinal reflex depressing and adrenergic α-blocking effects.

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