Effort toward finding some integrative functions in the cortical projection areas of the auditory systems has been made by several investigators. Raab and Ades (1) have reported that temporary amnesia for the learned habit is founded after bilateral ablation of the auditory cortex, but the habit is readily relearned. On the other hand, Neff et al. (2) have demonstrated that bilateral ablation of auditory cortex in the cat does lead to a lasting deficit in ability to localize sound in space. They have suggested following hypotheses: 1) an intact auditory cortex is necessary in order that the relationship between auditory signal and food reward may be learned, 2) an intact auditory cortex is essentially for maintenance to attention to an auditory signal, and 3) an intact auditory cortex is necessary for accurate localization of sound in space. However, the results have failed clearly to single out any of these. Lilly (3) and Lilly and Cherry (4) have shown the patterns of spontaneous electrical activity and those evoked by acoustic stimulation in the auditory cortex of the cat by means of a recording technique which gives simultaneous samples of the electrical activity from 25 electrodes on the cerebral cortex. From the observations under light and deep anesthesia, they have demonstrated that there is a certain validity to the accepted subdivision of auditory cortex, although this may have been overplayed in the past because most workers have used deeply anesthetized animals as the standard preparation.
Effects of anesthetics on the spontaneous activity and the evoked responses in the auditory cortex have also been shown by Reinberger and jasper (5), Brazier (6), Kiang et al. (7) and Pradhan and Galambos (8). It is generally known that most of anesthetics or hypnotics produce behavioral excitement in the induction phase. However, there is scarcely any systematic study for the relationship between the cerebral acoustic activity and infused doses of the anesthetics. The present experiments were designed to observe the effects of the central depressants continuously and intravenously infused on the spontaneous electrical activity and the response of the auditory cortex to acoustic stimuli in order to analyze the cortical or subcortical mechanism of hearing.

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The sympathetic nature of the hypogastric innervation of the ductus deferens of guinea-pig has been concluded by Hukovic (1) from the results that the contractile response of the isolated ductus deferens to stimulation of the hypogastric nerve is enhanced by the addition of noradrenaline and is abolished by the previous reserpinization of the animal. In the same line Boura et al. (2) and Bentley (3) have shown that the response is abolished by the addition of reserpine, guanethidine and bretylium. The enhancement of the response by the addition of carbamyl-choline has been shown by Bentley. Boyd et al. (4) and Burn et al. (5) have demonstrated the enhancement of the response by the addition of eserine and various adrenolytics. The potentiating effect of the adrenolytics has been explained by the anticholinesterase activity of the drugs. The transmission failure of the sympathetic nerve impulse in the preparation by hemicholinium has been shown by Chang and Rand (6) and Bentley (3). The inhibition of the contractile response by the ganglionic blocking agents has been shown by Sjöstrand (7) and Bentley (3). Sjöstrand (8) has proved that the chronic denervation of the ductus deferens does not affect the level of noradrenaline in the tissue. He has further indicated that the cholinergic mechanism of impulse transmission in the preparation is responsible for the release of the endogenous noradrenaline.
The assumption that the peripheral cholinergic mechanism is involved in the sympathetic innervation of the ductus deferens of guinea-pig facilitated the current studies.

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Although the peripheral effects of reserpine are generally accepted, there is evidence to support the central action on the adrenal medulla (1-5). No depletion of tissue noradrenaline by 10-methoxydeserpidine (10-MD) has been reported in mice by Leroy and Schaepdryver (6). However, Higuchi et al. (7) have shown that the intravenous injection of 10-MD in rabbits depletes considerably the content of noradrenaline in the brain cortex, brain stem and heart, and of adrenaline in the adrenal medulla without manifesting sedation or diarrhea.
10-MD has recently been used clinically for the essential hypertension. Episode of the side effect that hyperemia and warm sensation of the face and neck manifest in some patients several hours after the oral administration has been reported (8). No such side effect has hitherto been reported in the case of reserpine. Therefore, the current report deals firstly with elucidation of action mechanism of the hyperemia and warm sensation in the face and neck caused by 10-MD, and secondarily with the pharmacological difference between reserpine and 10-MD. The results in the present experiments have shown that though reserpine produces a marked elevation of the ear temperature followed by a steady fall of the rectal temperature, 10-MD elicits a similar elevation of the ear temperature attended with no change in the rectal temperature in rabbits.

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Among Oriental peoples the panacean use of Panax ginseng persists today as it has for centuries. Physicians in some areas of the Near East dispense this substance in powder, pill and tincture form and adhere to beliefs in its curative and “tonic” properties [Schultz (1)]. This widespread popularity and use have prompted a number of studies to determine possible pharmacological foundations for its continued employment.
Evidence has been advanced to indicate that ginseng stimulates the central nervous system and respiration [Petkov (2)], stimulates gastric and intestinal motility [Yoon (3)], corrects nutritional disorders [Myerhoff (4)], and blocks the hyperglycemic response to adrenaline [Kondo (5)]. Regarding the actions of ginseng on mean arterial blood pressure, the reports of Kim (6), Petkov (2), Hwang (7) and Park (8) indicate that the primary effect of ginseng is depressor followed by pressor in a variety of intact animals. Since the physiological basis of this response is uncertain, we have attempted, with modern instrumentation, to determine the extent of cardiac and/or vascular participation in the blood pressure response to ginseng administration.

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Since Handovsky (1) observed that intravenous administration of small amounts of acetaldehyde in anesthetized dogs produced a sharp rise in blood pressure and cardiac acceleration, many investigations have been done on the cardiovascular effects of acetaldehyde. Nelson (2) showed that acetaldehyde, given intravenously, had a pressor activity resembling epinephrine, and that this pressor response was markedly potentiated by cocaine and it was not due to the liberation of epinephrine from the adrenal glands. Christensen (3) reported that the action of epinephrine upon the blood pressure was duplicated by acetaldehyde in an amount “100 times larger” and the pressor response to acetaldehyde was reversed by an adrenolytic drug, C-7337, in dogs under pentobarbital anesthesia. Feingold (4) reported that the pressor response to acetaldehyde in dogs was not wholly due to the release of epinephrine from the adrenals and was reversed by an adrenergic blocking drug SY-28, when the bilateral adrenal vessels were ligated. Seibert et al. (5) found that the pressor response to acetaldehyde in dogs was blocked by dibenamine and by Priscoline. Wingard et al. (6) carried out a long-range study on the actions of aldehydes and found that the blood pressure responses of acetaldehyde were qualitatively quite similar to epinephrine.
Recently Eade (7) has reported that in spinal cats treated with reserpine acetaldehyde caused a fall in blood pressure, and in the normal animals the sympathomimetic aldehydes appeared to exert a part of their action upon cardiovascular system by the release of catecholamines from tissue stores other than the adrenal medulla. Further, he has found that the releasing action of the aldehydes appeared to differ from that of tyramine. However, he did not definitely describe the mechanism or mode of action of acetaldehyde. Romano et al. (8) and Eade (7) suggested that the nature of the catecholamine released by the aldehydes in normal animals was more like that of norepinephrine than epinephrine. However, the findings that the pressor response to acetaldehyde is reversed by pretreatment with dibenamine in normal spinal cats, and the depressor response to this drug is observed in chronically reserpinized spinal cats are not fully explained only by the action of acetaldehyde releasing norepinephrine.
We have performed pharmacological studies on acetaldehyde for several years. Some years ago, Yokokawa (9) in this department investigated the cardiovascular actions of acetaldehyde. The effect of acetaldehyde on cardiovascular system may explain some pharmacological actions of alcohol, especially acute after-effects of alcoholic beverages (10).
The present investigation was carried out in order to correlate the pressor response and the nictitating membrane response of the spinal cat to acetaldehyde and to elucidate the mechanism of action of acetaldehyde on the cardiovascular system. In this study the pressor and the nictitating membrane responses to acetaldehyde were compared with those caused by tyramine, epinephrine and norepinephrine.

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It is well known that the animal, after a large dose of isoniazid, has a short series of clonic movements followed by a tonic convulsion with a sustained contraction of all muscles. The seizures are characterized by a relatively prolonged interval of time between the administration of the drug and the onset of epileptiform seizures (1, 2).
In our preceding paper (3), it has been described that this latent period differs with routes of administration and may be dependent on the isoniazid level in the central nervous system.
Assuming that there existed a critical concentration in regard to the brain level of isoniazid, it would reasonably be considered that the convulsion does not appear until the brain level exceeds this critical point, even if an animal received isoniazid sufficient to cause a maximal seizure.
Many reports, however, revealed that isoniazid undergoes a considerable metabolic change within a few hours after the administration to man and experimental animals (4, 5).
Therefore, it is felt that an investigation of the distribution and metabolic pattern of isoniazid in the animals under the drug-induced seizures may serve to determine if any correlation existed between the convulsive action and the metabolism of this compound.
The present paper describes distribution experiments in cats receiving a convulsive dose of isoniazid and also describes metabolic experiments carried out with mice receiving ¹⁴C-labelled isoniazid.

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The pharmacological effects of xylopinine (2, 3, 10, 11-tetramethoxy-5, 6-13, 13a-tetrahydro-8-dibenzo(a-g)quinolizine) in rabbit, cat and dog have been reported elsewhere (1, 2). Xylopinine induced a long-lasting fall of blood pressure and peripheral adrenolytic and sympatholytic effects. Furthermore, the sedative and potentiating effects of xylopinine on barbiturate sleep in mice were also observed. The electroencephalographic studies of xylopinine in the current report confirm that the drug depresses the activity of the brain stem reticular activating system, the specific and non-specific thalamocortical projection systems and the hypothalamic activating system. Further, there is a possibility that xylopinine exerts its central depressive effect by virtue of its adrenolytic activity as chlorpromazine presumably does (3). Although chemical structure of xylopinine closely related with those of reserpine and tetrabenazine, xylopinine does not affect the content of brain noradrenaline (4), and its pharmacological effects are not modified by pretreatment of animals with monoamine oxidase inhibitors (1).
The electroencephalographic studies of reserpine, decaserpine and tetrabenazine have been described elsewhere (5-7). Reserpine and decaserpine produced a biphasic response in unanesthetized rabbit. The first appearance of the resting waves in the spontaneous EEG for 30 to 60 minutes was followed by the appearance of the arousal waves. The initial responses of the EEG to the drugs were likely to derive from the endogenously liberated noradrenaline. The manifestation of the resting waves in the EEG by the intravenous noradrenaline has already been demonstrated (8, 9). However, the manifestation of the arousal waves by the intravenous or intracarotid injection of catecholamine has also been shown (10, 11). These evidences support the biphasic response of catecholamine on the spontaneous EEG.

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Though the use of thyroid hormone in the treatment of hypercholesterolemia in the humans received wide acceptance, its practical use is limited by the high incidence of angina attack and by the influence through the augmented rate of basal metabolism. 3, 5, 3'-Triiodothyronine (T₃), 3, 5, 3'-triiodothyroacetic acid (Triac), 3, 5, 3'5'-tetraiodothyroacetic acid (Tetrac) and other possible metabolites of thyroxine were reported to suppress serum cholesterol levels within the range of doses which did not produce concomitant rise in basal metabolic rate (1-4). Through these experiments the evaluation of other derivatives became one of the most attractive projects not only for the clinical but also the experimental studies for attempting to separate the cholesterolytic property from the effect on the basal metabolism by changing the chemical structures. Among them, 3, 5, 3'-triiodothyroformic acid (T₃-F) was reported by Boyd and Oliver (3, 4) as a possible metabolite of thyroxine. Kumaoka et al. (5) demonstrated that 3, 5, 3'-triiodo-4'acetyl-thyroformic acid (TBF-43) produced a moderate cholesterolytic effect without much increase of basal metabolic rate in cases of essential hypertension and myxedema when 10 to 50 mg were prescribed daily. Acute and subacute toxicities of the compound were presented by Aramaki et al. (6) and Kajihara et al. (7). They reported that subacute oral administration of TBF-43 in the daily doses above 40 mg/kg caused a retardation of growth in rats. Furthermore, the autopsy study proved an increase in the weight of the parenchymal organs, especially the heart, kidney and adrenal gland.
The present report deals with the chronic oral toxicities of TBF-43 in the rats and rabbits fed on the standard diet or high-cholesterol diet.

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It was previously reported (1-3) that the shock-like fall in blood pressure of the cat produced by an intravenous injection of Congo red was partly due to an increase in concentration of serotonin (5-HT) in the blood plasma. It was also noted that congo red caused a reduction in number of blood platelets in the cat both in vitro and in vivo. It was, therefore, suggested that Congo red destroyed platelets to release 5-HT into plasma by an unknown mechanism.
The present work was undertaken with the intent of investigating the mechanism of 5-HT release. In addition, the role of 5-HT released during the colloid shock was investigated, using several colloids including congo red, inulin and mastix.

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The anaphylactic histamine release from guinea-pig and rat lung tissues was completely or largely depressed by oxygen lack, respiratory inhibitors and uncouplers of oxidative phosphorylation when the incubation medium was devoid of glucose (1-7). Similar inhibition has been found of compound 48/80-induced histamine release from rat lung tissue and of degranulation of rat mesentery mast cells (6, 8, 9). Since these inhibitions were largely overcome by the presence of glucose (4-9), and phlorizin (10) and 2-deoxyglucose (7) inhibited these glucose-dependent release of histamine, glycolysis should be considered to take part in supplying the energy required for these processes. Chymotrypsin is also known to cause histamine release (11) and degranulation of mast cells (11, 12), and the latter action is also blocked by anoxia and glucose has a preventive effect on this block.
There are a number of works demonstrating the histamine-releasing or degranulating effect of compound 48/80 and some other agents including anti-serum (13) on isolated mast cells or mixed cell suspension taken from rat peritoneal fluid. However, the observations relevant to glucose dependency are all based on the experiments with excised tissues but not with isolated cells, because an anaerobic experiment with isolated mast cells seems to have not yet been successful. Thus, Keller and Beeger (14) reported that the introduction of nitrogen gas into the cell suspension resulted in a complete destruction of mast cells; Moran et al. (15) were unable to demonstrate an inhibition of 48/80induced amine release from mixed peritoneal cells by incubating in their supposedly oxygen-free atmosphere in the absence of glucose.
In the present experiments, with isolated mast cells, the glucose-dependent degranulation by compound 48/80, α-chymotrypsin and anti-serum is demonstrated under nitrogen anaerobiosis with success, and the effects of some inhibitors including phlorizin and 2-deoxyglucose are studied. Observations in aerobiosis are also described.

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