The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 19 , Issue 3
Showing 1-22 articles out of 22 articles from the selected issue
  • RYUICHI KATO, AKIRA TAKANAKA, KINICHI ONODA, YOSHIHITO OMORI
    1969 Volume 19 Issue 3 Pages 331-342
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    There is considerable evidence in the literature that the rate of drug absorption from gastrointestinal tract is one of major factors for the determination of drug action (1-3). In a previous paper, it was reported that the serum concentration of aminopyrine or sulpyrine after oral administration in rabbits showed marked difference according to the preparative form of the drugs (4). The serum concentration of aminopyrine or sulpyrine in rabbits was higher when the drugs were given as the aqueous solution than that when the drugs were given as the syrup form or tablet. The purpose of present investigation was to study a possible mechanism of the modification in the absorption and serum level of the drugs given as the syrup form.
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  • HIKARU OZAWA, KAZUNOBU SUGAWARA
    1969 Volume 19 Issue 3 Pages 343-353
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Ozawa et al. have reported the effects and the structure-activity relationship of mono-alkylguanidines on the smooth muscle preparations innervated by the sympathetic nerve, on the cardiac activity and on the blood pressure (1). In the paper, they concluded that the actions of monoalkylguanidino compounds were different between the compounds with a small substituent and a bulky substituent, and that the activity increased according to the carbon numbers. These results coincide with the report by Ozawa et al. (2) on the effect and the structure-activity relationship of monoalkylguanidines in the skeletal muscle preparation.
    In the present paper, authors investigated in more detail the action of hexylguanidine which has the most bulky carbon chain among these compounds and revealed a most striking pharmacological action resemble to cocaine.
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  • YOSHITOSHI KASÉ, MIKIKO KATAOKA, TAKESHI MIYATA
    1969 Volume 19 Issue 3 Pages 354-362
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Piperidine, possessing acetylcholine- and nicotine-like properties not only in the peripheral nervous system (1-3) but also in the central nervous system (4), has been described to be one of normal constituents in urine (5-7) and the mammalian brain (8-10). Recently, it has also been demonstrated in vitro that piperidine can be produced from pipecolic acid by decarboxylation in the presence of the brain tissue (11). It seems to be of great interest to study the distribution and physiological role of piperidine in living body. Therefore, it has been tried in our laboratory to develop a method applicable for the determination of micro amounts of piperidine in living materials. The present authors have already reported a quantitative determination method for piperidine by making use of color reaction due to the production of copper piperidino-dithiocarbamate (12) ; this method is sensitive but not specific for piperidine, and separation of the amine from other aliphatic amines is difficult. Recently, Asatoor (13, 14) has reported a method which is applicable for separation and detection of aliphatic and alicyclic amines in urine, however, this is available just for qualitative analysis.
    The present paper deals with a new method which has been developed by further improvement of Asatoor's procedure in order to make the procedure fit the quantitative analysis of micro amounts of piperidine. Using this method, furthermore, the average amounts of piperidine in biological materials such as the pig brain and the urine of normal healthy students and schizophrenic patients, as a representative of psychoses, are also described.
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  • MASASHI SASA, NAOHISA FUKUDA, SHUJI TAKAORI
    1969 Volume 19 Issue 3 Pages 363-372
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Informations for the neural mechanism of pain sensation are still insufficient. Haugen and Melzack (1, 2) have shown that the afferent fibers most closely related to pain perception caused by electrical stimulation of the tooth pulp project to the sensory cortex through the trigemino-bulbo-thalamic tract, but not via the trigeminal lemniscus. The significance of participation of the thalamic intralaminal nuclei in pain mechanism has been emphasized by Gangloff and Monnier (3) and Albe-Fessard and Kruger (4). However, the concept of a specific pain center in the brain is considered to be totally inadequate, since the thalamus, hypothalamus, brainstem reticular formation and parietal cortex are all implicated in pain perception (5).
    In the previous paper (6), it was presumed that 1) the hypothalamus formed closed circuits with other brain structures, and 2) the circulation of impulses within these circuits might contribute to the central regulation of sensory mechanism. In the present experiments, the effects of aminopyrine and phenylbutazone on the evoked potentials in the sensory cortex and posterior hypothalamus as well as on the responses of unit discharges in the posterior hypothalamus and trigeminal nuclei to afferent electrical stimulation of the inferior alveolar nerve were studied in attempt to find the mode of action of these analgesics in the central nervous system.
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  • MASASHI SASA
    1969 Volume 19 Issue 3 Pages 373-385
    Published: 1969
    Released: February 02, 2007
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    The primary relay nuclei of the afferent sensory pathway have been demonstrated by Fujita et al. (1, 2) as one of the sites of action of morphine in the central nervous system. They have shown that the evoked potentials in the spinal cord of the cat caused by afferent stimulation of the splanchnic, phrenic and inferior cardiac nerves are depressed by intravenous injection of morphine. However, Takagi et al. (3) have postulated that the inhibitory effect of morphine on the spinal cord derives from an activation of inhibitory mechanism in the midbrain reticular formation rather than from a direct action. The experiments of Mizoguchi (4) in the dog have demonstrated that morphine suppresses the evoked potentials in the Nucl. tractus spinalis n. trigemini but does not affect those in the Nucl. sensorius superior n. trigemini caused by electrical stimulation of the tooth pulp. The neurons in the former nucleus are known to receive pain and temperature impulses, while those in the latter nucleus to receive tactile impulses (5). Therefore, the experimental results presented by Mizoguchi (4) are well compatible with an explanation of the site of analgesic action of morphine.
    On the other hand, by using microelectrode technique Kruger and Michel (6) could not find any neuron activity uniquely sensitive to noxious stimuli in the Nucl. tractus spinalis n. trigemini, but they found that all tactile neurons in that nucleus responded well to painful stimuli.
    The present experiment is an attempt to elucidate the mode of action of morphine upon the unit discharges in the Nucl. sensorius superior and Nucl. tractus spinalis n. trigemini of the cat by means of microelectrode technique.
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  • ELDON M. BOYD, C. J. KRIJNEN
    1969 Volume 19 Issue 3 Pages 386-393
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    In a study of the clinicopathologic syndrome of toxicity to phenacetin at the range of the acute, oral LD50, Boyd in 1959 (1) used adult female rats and reported the LD50±SE to be 1.65±0.35 g/kg body weight. In 1968, Boyd and Hottenroth (2) studied the toxicity of phenacetin at the range of the oral LD50 (100 days) and reported the acute oral LD50±SE in young male albino rats to be 4.14±0.71 g/kg. Boyd and Hottenroth (2) also reported that female rats were more sensitive to the lethal effects of daily administration of phenacetin than were male rats. In a comparison of the acute oral LD50 in young male and female rats, sex of the animals was found to have no influence on the median lethal dose. To find a reason for these apparently contradictory results, it was decided to measure the clinicopathologic syndrome of toxicity to single oral doses of phenacetin, after methods reviewed by Boyd (3), in male and female albino rats from the age of weaning to that of middle-aged, 1 to 1.5 year old, adults. Over this interval of time, certain organs comprise changing percentages of body weight. Since values for the LD50 are normally expressed as g per kg body weight, it was decided to calculate LD50 values in addition as g/kg organ weights. Any organ in which variation in the LD50 so calculated was less than variation calculated as g/kg body weight, could be concluded to be more concerned with tolerance to lethal doses of phenacetin than is total body weight.
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  • HIDEOMI FUKUDA, KAZUO WATANABE, TSUGUTAKA ITO
    1969 Volume 19 Issue 3 Pages 394-400
    Published: 1969
    Released: February 02, 2007
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    Pharmacological and histological studies (1 — 4) have been made on the effect of the toxic extract from Lyonia ovalifolia var. elliptica (Ericaceae) or lyoniol-A (5), an amyostatic component isolated from the plant. In the previous study (4), we found that intravenous injection of 2 mg/kg of lyoniol-A induced the responses with long latencies in the evoked electromyogram (EMG) of young chicks. In the present study, an experiment was made to elucidate the reflex responses induced by lyoniol-A in the evoked EMG of chicks in comparison with the actions of strychnine and pentylenetetrazol.
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  • AKINOBU NAGAOKA, KENZO KIKUCHI, YOSHITOMO ARAMAKI
    1969 Volume 19 Issue 3 Pages 401-408
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    A variety of experimental hypertensions in rats has been available for the evaluation of the anti-hypertensive agents as well as for the mechanism studies of essential hypertension. The spontaneously hypertensive (SH) rat with 100 per cent incidence of heredity has been separated from the Wistar rats (1). Though the hypertension develops in the early stage without certain etiology, the animals in the advanced stage exhibit the vascular lesions such as periarteritis nodosa, nephrosclerosis and cardiac lesions (2-5). Recently, Okamoto et al. (6, 7) and Matsumoto (8) have indicated further some involvement of neural factors in development and maintenance of the hypertension.
    In order to elucidate pharmacologically the mode of the hypertension in the SH rats, the depressor responses to the anti-hypertensive agents were observed comparatively between in the SH and normotensive (N) rats.
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  • SHOICHI IIDA, MORIO KANNO, KATSUYA NAKAMURA
    1969 Volume 19 Issue 3 Pages 409-417
    Published: 1969
    Released: February 02, 2007
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    Cochin and Kornetsky (1) showed that tolerance to the effects of a single injection of morphine in the rat as measured by the hot plate reaction could be demonstrated for periods up to one year following that single injection. Thus, they postulated that tolerance to narcotic drugs might well be an immune phenomenon or a mechanism resembling the antigen-antibody reaction.
    Later, Kornetsky and Kiplinger (2, 3) attempted a passive transfer of a hypothetical factor of tolerance in serum from morphine-tolerant animals (rat, dog, monkey and man) to nontolerant animals (mouse). Although they were unsuccessful in transferring the tolerance, they succeeded in demonstrating the presence of certain transferable factors in the serum of morphine-tolerant animals, since under condition of those studies, potentiation of the depressant and an analgesic action of morphine was observed. The role of the potentiating substance in the serum of the morphine-tolerant animal and the mechanism by which it potentiates morphine are as yet unknown.
    On the other hand, Kornetsky and Cochin (4) reported that serum from morphinetolerant rabbits attenuated morphine analgesia in mice and they assumed that the immune mechanisms involved may partially account for some of the phenomena associated with tolerance to morphine. Ungar and Cohen (5) also showed that administration of extracts of the brain taken from morphine-tolerant rats and dogs conferred tolerance on mice.
    The presence of the factors in the blood of morphine-tolerant animals that have attenuating or enhancing effects on morphine in nontolerant animals is an interesting finding, although the immune reaction hypothesis is no more than speculation.
    During a study of the effect of the treatment with a homogenate of the brain from alcohol-tolerant rabbits, on the duration of alcohol anesthesia following the intravenous injection of a test dose of alcohol, it was noted that an increased sensitivity and/or a decreased or a biphasic change in the sensitivity to alcohol was observed depending on the individual rabbit.
    Based on these conflicting evidences the present investigation was undertaken to define the change of sensitivity to alcohol using the normal rabbit as the recipient and the donor species.
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  • KEIJIRO TAKAGI, SUSUMU OKABE, RYUICHI SAZIKI
    1969 Volume 19 Issue 3 Pages 418-426
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Several methods have been reported to produce an experimental chronic ulcer in the rat, such as thermal ulcer by Skoryna et al. (1, 2), clamping-cortisone ulcer by Umebara et al. (3), and methylcholanthrene ulcer by Lauren et al. (4). In these methods thermal and clamping-cortisone ulcers seem to be valuable tools in investigation of the healing process of gastric ulcer, because of the relatively long period of its persistence and closer histologic resemblance to human peptic ulcer. However, both methods include the undesirable procedure such as the incision of glandular portion of stomach in order to perform the thermocautery of the innersurface of stomach in the former method and the consecutive administration of cortisone acetate for 8 days after the gastric operation in the latter. On the other hand, Robert and Selye (5) have reported the method to evoke an ulcer by an injection of formalin solution into the rat stomach wall itself. We also tried the same procedure and found the gastric necrosis corresponding to the injected area. However, the necrotic tissue did not disappear from the stomach wall even 6 days after the operation so that the so-called gastric ulcer was not produced. Then we injected the acetic acid solution, which is well known to injure the gastric mucosa (6) or to evoke inflammation in rat paw in our laboratory (7), into the rat stomach wall and found the definite gastric ulcer having resemblances to the human peptic ulcer at gross and microscopical observation. This paper deals with the studies of the healing process of the produced ulcer and the usefulness for the assay method of the curative drugs of gastric ulcer.
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  • S. BHAGAT, A. DASS, S. ARORA, R.K. SANYAL
    1969 Volume 19 Issue 3 Pages 427-430
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Amongst the varieties of procedures which have been adopted for controlling birth rate, the intra-uterine contraceptive device (IUCD) has a very prominent place. The IUCD has been found to be effective as a contraceptive device in several studies (1 — 4) and several theories have been proposed to explain its mechanism of action. Recently it has been suggested that the presence of IUCD in the rat uterus leads to an increase in the local mast cell population, and this may be an important factor in its mechanism of contraceptive action (5). It was further proposed that increase in number of mast cells might be directly responsible for prevention of nidation, as injection of comp. 48/80 a compound which is known to disrupt mast cells, at times allowed conception to take place even in the presence of the device.
    In view of the importance of the problem, the mast cell population in human uterus after insertion of the IUCD was studied.
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  • KEIJIRO TAKAGI, KOICHIRO KAWASHIMA
    1969 Volume 19 Issue 3 Pages 431-437
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    It has been reported that many anti-inflammatory drugs employed in the treatment of rheumatic disorders cause various gastrointestinal disturbances, such as haemorrhage and the development or reactivation of peptic ulcer. The mechanisms involved are not understood precisely, but they may include stimulation of gastric acid secretion and decrease in the resistance of the local gastrointestinal mucosa (1).
    Serum proteins, albumin and globulin, have been found in gastric juice (2-4). A hypothesis that transudation of serum proteins from capillaries to the interstitial spaces and thence into the lumen of the stomach is a normal physiological process was proposed by Hollander and Horowitz (5). It has been shown that clinically a massive leakage of serum proteins into the stomach occurs often in gastric cancer, Menetrier's disease, and in some cases of gastric atrophy (6, 7). In addition, experimentally increased plasma output was seen in the canine stomach irrigated with fatty acids or salicylates (8).
    In the present study, in order to find some relationships between gastric disturbances and chages in capillary permeability of the gastric mucosa, we investigated the effects of anti-inflammatory drugs, that is, aspirin, cinchophen, cortisone, indomethacin, and phenylbutazone, and three plant extracts which have anti-inflammatory or anti-peptic ulcer activities (9-12), on the output of plasma and the volume of gastric juice.
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  • RYUICHI KATO, KINICHI ONODA, MICHIKO TAKAYANAGI
    1969 Volume 19 Issue 3 Pages 438-450
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    It has been reported that the activities of drug-metabolizing enzymes of liver microsomes are inhibited by different kind of drugs (1). SKF 525-A (β-diethylaminoethyl-diphenylpropylacetate HCl) was discovered for the first time and it has been known as the most popular and typical inhibitor of microsomal drug-metabolizing enzymes (2-4), while DPEA (2, 4-dichlorophenylphenoxyethylamine HCl) has been known as the most potent inhibitor (5-6). Moreover, Kato et al. (1, 7, 8) reported that the inhibitors of the microsomal enzymes, such as SKF 525-A, DPEA and MG 3062 (phenyl-(4-chlorophenyl)-4-piridylmethanol) increase the activities of drug-metabolizing enzymes, on the other hand, the inducers of the microsomal enzymes, such as chlorcyclizine, glutethimide and phenaglycodol inhibit the activities of drug-metabolizing enzymes.
    It has been established that a number of commonly used drugs of high lipid-solubility inhibit the activities of drug-metabolizing enzymes and the in vivo metabolism of various drugs (1, 9-11). The inhibition in the metabolism of drugs seems to be popular phenomenon in combined administration of more than two drugs and sometimes even mutual inhibition may be occurred, therefore, these phenomena are important for the evaluation of drug activity and for the determination of dosage schedule in drug therapy (1). However, the mechanism by which many drugs produce the inhibition of the activities of drugmetabolizing enzymes has not yet been elucidated (12, 13). Netter (14) observed that SKF 525-A noncompetitively inhibited the O-demethylation of o-nitroanisole. In contrast, McMahone (5) reported that SKF 525-A and DPEA competitively inhibited the N-demethylation of butynamine. Moreover, Rubin et al. (11) reported that SKF 525-A competitively inhibited the N-demethylations of morphine and ethylmorphine. In a previous work (15), we briefly reported that N-demethylation of aminopyrine and hydroxylation of hexobarbital in rat liver microsomes were competitively inhibited by SKF 525-A, while they were noncompetitively inhibited by SKF 525-A in rabbit liver microsomes.
    The present communication is concerned with the species difference in the inhibition of various pathways of drug metabolisms in liver microsomes by different inhibitors. The differences in the type and potency of the inhibition between rats, rabbits and mice may offer some insight for the mechanism of the inhibition of drug-metabolizing enzymre.
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  • SUKEHIRO CHIBA
    1969 Volume 19 Issue 3 Pages 451-459
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
    Our previous observation in the cat with implanted electrodes has demonstrated that 2-ethyl-4-ethylamino-6-methoxy-s-triazine (EEM) induced a long-lasting electroence-phalographic (EEG) activation and tachypnea. While the animal was initially excited as indicated by some restlessness, salivation, defecation and occasionally vocalization, thereafter it showed depressive behaviors such as mild muscular weakness, decreased locomotor activity, decreased responsiveness to extroceptive stimuli and lying prostrate throughout the EEG activation (1). Furthermore, the sympathetic excitement induced by EEM in curarized cat persisted for a considerably long period but always outlasted its EEG change (2). In the rat, this agent produced a cataleptic sign and disrupted the conditioned avoidance behavior without failure of the escape response. Despite activating both the electrical brain activity and the autonomic nervous function in such a manner, the motor function and the conditioned behavior were moderately depressed. Our preceding papers have stressed the important roles of the brain stem for the EEG activation and that of the posterior hypothalamus for the sympathetic excitements.
    The present experiments were carried out to study the effect of EEM on spinal reflex and muscle contraction in an attempt to clarify the mechanism of its motor depression.
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  • SURENDRA S. PARMAR, S. NAGAR
    1969 Volume 19 Issue 3 Pages 460-462
    Published: 1969
    Released: February 02, 2007
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  • AKINOBU NAGAOKA, KENZO KIKUCHI, YOSHITOMO ARAMAKI
    1969 Volume 19 Issue 3 Pages 462-464
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
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  • YOSHIMI MISU, TAKAO KUBO
    1969 Volume 19 Issue 3 Pages 464-465
    Published: 1969
    Released: February 02, 2007
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  • MASAMI DOTEUCHI, HIRONORI NAKANISHI, HIDEO TANAKA
    1969 Volume 19 Issue 3 Pages 466-467
    Published: 1969
    Released: February 02, 2007
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  • PAWAN S. CHAUHAN, S.K. CHAUDHURY, REKHA GUHA, C.K. ARORA
    1969 Volume 19 Issue 3 Pages 468-470
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
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  • RYUICHI KATO, AKIRA TAKANAKA, KINICHI ONODA, YOSHIHITO OMORI
    1969 Volume 19 Issue 3 Pages 470-472
    Published: 1969
    Released: February 02, 2007
    JOURNALS FREE ACCESS
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  • A. AHMAD, B.N. DHAWAN
    1969 Volume 19 Issue 3 Pages 472-474
    Published: 1969
    Released: February 02, 2007
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  • YOSHIO AIZAWA, KENJI YAMADA
    1969 Volume 19 Issue 3 Pages 474-476
    Published: 1969
    Released: February 02, 2007
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