The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 18, Issue 4
Displaying 1-21 of 21 articles from this issue
  • TETSUO SATOH
    1968 Volume 18 Issue 4 Pages 373-380
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    The formation of complex between protein and thiamine propyl disulfide (TPD) has been studied by many investigators. Higher radioactivity in rats treated with TPD-S35 (outer) was found in blood (1), and when venous blood of normal healthy rabbit was incubated with TPD-S35 (outer), the radioactivity was concentrated in serum albumin fraction (2). As illustrated in Fig. 1, TPD contains S-S bond which is reduced to produce both propylmercapto moiety and thiol type of thiamine. Utsumi et al. (3) indicated the formation of complex between albumin and propylmercapto moiety dissociated from TPD, and their successive paper (4) described binding of TPD to bovine serum albumin. Reduction of TPD in incubation with blood cell was responsible for SH groups in blood (5), and Kawasaki el al. (6) suggested the binding between TPD and SH enzymes, papain and alcohol dehydrogenase. On the other hand, recent studies by Maeno and Feigelson (7) have shown the chemical properties of the reductive activation of liver tryptophan pyrrolase (TP) by ascorbate, GSH and dithiothreitol, and implicated that one or more SH groups were involved in TP as binding site for tryptophan. In the previous paper (8), six thiamine derivatives, i.e., thiamine-mono, -di and -triphosphate, S-benzoylthiamine-mono, -di and -tri phosphate were used to examine their effects on TP in the mechanism of energy dependent activation by ATP-Mn++ system reported by Pitot and Cho (9) and no significant effects were observed. It seemed possible to speculate that these phosphates of thiamine or S-benzoylthiamine have little effect on TP because of involving no S-S groups in their molecules. Since preliminary experiments with homogenate showed that effects of TPD on TP varied on pH of the incubation mixture, the purpose of the present study is to investigate the effects of TPD on TP.
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  • RYUICHI KATO, AKIRA TAKANAKA
    1968 Volume 18 Issue 4 Pages 381-388
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    Many lipid soluble compounds are metabolized by liver microsomes in the presence of oxygen and NADPH (1, 2). It has been considered that NADPH oxidizing system of liver microsomes is the responsible component for the oxidation and reduction of drugs (1-3). The metabolisms (oxidation and reduction) of drugs by liver microsomes are altered by diet, age and sex as well as by some unphysiological conditions (4-8). The alterations in the metabolisms of drugs are often accompanied with similar alterations in the activities of NADPH-linked electron transport system of liver microsomes (3, 4, 8-10). In a previous paper we reported a marked age differences in the oxidation of drugs, such as, hexobarbital, pentobarbital, meprobamate and carisoprodol by liver microsomes in the female rats (6). The activities of drug oxidations are almost zero at the birth and then rapidly increased upto 30 days, but the activities again decreased slightly with maturing in female rats. On the other hand, the activities in male rats are still increased with maturing and then slightly decreased (11). The purpose of present studies is the determination of the activities of drug-oxidizing and -reducing systems in old rats (about 600 days old) in comparison with young adult rats (about 100 days old). Moreover, it is of interest to investigate whether or not decreased activities in drug-oxidation and -reduction in old rats is related to those of NADPH-linked electron transport systems of liver microsomes. Many activities of drug oxidation show a clear sex difference and the activities are dependent on male sex hormone (6, 12). In the present experiments, therefore, the male and female rats were used for the study of the effect of male sex hormone in old rats.
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  • RYUICHI KATO, AKIRA TAKANAKA
    1968 Volume 18 Issue 4 Pages 389-396
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    It is well known that the effects of some drugs in old animals quite differ from those in young animals. For example, Farner and Verzar (1) observed that the action of amphetamine to increase moter activity was more marked in young rats than in old rats and the action of hexobarbital to antagonized against the amphetamine action was more effective in old rats than in young rats. Moreover, the duration of hexobarbital anesthesia was longer in old rats than in young rats (2). Similarly, Petty and Karler (3) observed that anticonvulsive activity of acetazolamide and phenobarbital was more marked in old rats than in young rats. However, there is no study on the mechanism of such altered drug response in relation to the rate of drug metabolism. In a previous paper it was reported from our laboratory that the activities in the oxidation and reduction of drugs and NADPH-linked electron transport system in liver microsomes of male and female rats were progressively decreased with aging (4). It is, therefore, of interest to investigate whether or not the metabolism in vivo of various drugs is decreased in old rats in accordance with the decrease in the metabolic activities of liver microsomes observed in the in vitro experiments. Moreover, the relationship between the effects of drugs and the rate of in vivo metabolism of drugs in the old rats was studied.
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  • HIDEO NISHIGORI, YOSHIO AIZAWA
    1968 Volume 18 Issue 4 Pages 397-405
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    Aizawa and Mueller (1) reported that phospholipid biosynthesis in ovariectomized rat uterus is much more accelerated by a single injection of estradiol. Recently, in our laboratory, the acceleration of phospholipid metabolism by estradiol treatment was examined by using various 32P compounds as substrate, and it was suggested that the biosynthesis of phosphorylethanolamine and phosphorylcholine in rat uterine tissue was much stimulated by the administration of estradiol (2). In the present work, metabolism of choline-1, 2-14C, DL-serine-3-14C, and ethanolamine-2-14C, which are all components of phospholipid, was investigated in uterus and liver of ovariectomized rat in vitro. Furthermore, the effect of estradiol on the incorporation of these compounds into phospholipid in liver was compared with rat uterus since there is a sex difference in lecithin formation and more lecithin is synthesized by stepwise methylation of phosphatidylethanolamine in female rat (3-5).
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  • GORO HAYASHI, SEIICHI NURIMOTO, YUZO NOGUCHI, HIROSHI KUGITA, YOSHIO K ...
    1968 Volume 18 Issue 4 Pages 406-417
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    Many analogs of iso-pethidine have been synthesized and examined for their analgesic activities, which, however were found lower than those of meperidine (1, 2). The authors, studying pharmacological effects of N-transferred compounds of benzomorphan (3), found that some of 3-phenyl-piperidine derivatives possessed strong analgesic effectiveness, and investigated the relationship between chemical structures and biological activities (4, 5). Among them 1-phenacyl-2, 3-dimethyl-3-(3-hydroxyphenyl) piperidine hydrochloride (TA-306) showed the most potent analgesic effect and low toxicity. The compound did not suppress abstinence signs of the monkey physically dependent on morphine (6). In this report are described further studies of the analgesic activity of TA-306 and comparative pharmacological studies of the drug with morphine hydrochloride and meperidine hydrochloride.
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  • G. ACHARI, C.N. SINHA
    1968 Volume 18 Issue 4 Pages 418-420
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    Buglia (1) had observed that absence of calcium suppresses the rythmic contractions of intestine. Vanysek (2) stated that calcium chloride stimulates the circular and relaxes the longitudinal muscle in the excised intestine of the cat. Robertson (3) reported that deficiency of calcium produces hypertonicity of the colon. Later Jhonson (4) found that cooling and reduction of calcium ion reduced the spontaneous output of acetylcholine from the nerve endings in the wall of the intestine. Burn and Gibbons (5) had noted that the inhibitory effect of stimulating the periarterial nerves on the pendular movements of a loop of rabbit ileum depends on the concentration of calcium present. The inhibition due to stimulation was greatly increased, when the calcium concentration was raised from below normal to the normal concentration in the tyrode solution. Literature about the effect of calcium at different temperatures is not readily available. In the present work action of calcium ion on isolated rabbit ileum has been investigated at different temperatures.
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  • BRUNO SILVESTRINI, SILVANA BURBERI, BRUNO CATANESE
    1968 Volume 18 Issue 4 Pages 421-429
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    The reversibility of the rheumatoid process observed during hepatitis and jaundice (1) has been generally explained in terms of increased corticosteroidal activity, due either to retention of bile acids, which contain chemical nuclei of a steroidal nature similar to those of adrenal cortical hormones (2), or to the ability of bilirubin to displace corticosteroids from sites of protein binding (3). Little attention has been given to the possibility that different mechanisms are involved in the inhibition of inflammation which takes place during jaundice. Our interest in this problem was stimulated on reading that in rats ligature of bile duct brings about an inhibition of inflammatory lesions produced by Freund's adjuvant (4). This result led us to investigate the anti-inflammatory effect of jaundice by means of an experimental scheme analogous to that generally employed to evaluate antirheumatic drugs.
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  • YASUKO AMANO, SHUJI TAKAORI
    1968 Volume 18 Issue 4 Pages 430-435
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    It is well-known that antiphlogistics such as salicylates and pyrazolon derivatives have the multiple effects on tissue metabolism. These metabolic effects including inhibition of corticosteroid biotransformation, uncoupling of oxidative phosphorylation, glycogenolysis, alteration of electrolyte balance and inhibition of mucopolysaccharide biosynthesis seem to merit attention in relation to their antiphlogistic activities (1-3). Tanabe and his co-workers (4, 5) have shown that a death caused by larger doses of phenylbutazone and 5-n-butyl-l-cyclohexyl-2, 4, 6-trioxoperhydropyrimidine (BCP) is probably due to the decompensation of adrenocortical function, since repeated administrations of these agents produce the diffuse hemorrhage and proliferation of adrenal cortex in the rat. Korus et al. (6) have reported that in the inactivation process of cortisone phenylbutazone not only inhibits the transformation of the α, β-unsaturated ketonic group of ring A, but also the degradation of the α-ketolic side chain of ring D. However, Dirscherl and Lutzmann (7) have observed only the inhibitory effect of aminophenazone on the reduction of ring A. These studies imply that the retardation of cortisone biotransformation is a possible component of the antiphlogistic action of these drugs. Ban (8) has emphasized that the site of stimulating action of aminopyrine is located in the hypothalamus. The hyperglycemic effects of morphine (9, 10) and salicylates (11) have been shown to be dependent on the release of catecholamines from the adrenal medulla presumably through the activation of the sympathetic centers in the brain. Therefore, it is conceivable that antiphlogistics such as aminopyrine, phenylbutazone, BCP and indomethacin modify the carbohydrate metabolism through the adrenal functions. The present experiment is an attempt to discover the effects of single and repeated administration of these antiphlogistics on the level of blood glucose in the rat.
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  • N.K. DADKAR, S.K. DAMLE, B.B. GAITONDE
    1968 Volume 18 Issue 4 Pages 436-444
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    Antimetabolites have been used for some time in the treatment of malignant disorders. Farber et al. (1) used folic acid antagonists and, since then, a number of antimetabolites of purines and pyrimidines have been investigated. One of the important drawbacks of all such compounds is their toxicity to host cells due to non-specicity of action. An ideal drug, therefore, would be one which would have a preferential action on tumour cells. This would be possible if tumour cells were shown to have a distinct biochemical pattern different from that of the host cells. Gadekar and Sahasrabudhe (2) have put forward evidence that there is a relative preponderence of the hexose monophosphate (HMP) pathway activity in neoplastic tissue. On the basis of this suggestion, Sahasrabudhe et al. (3) have reported 2, 5-dicarbethoxy, 3, 4-dihydroxythiophane (dicetol) to be effective in blocking the HMP pathway preferentially in tumour tissue. They have also reported anticancer properties for this compound in transplanted fibrosarcoma in Swiss mice (2-4). Since the compound showed promising results in experimental cancer, it was decided to investigate some of its pharmacological actions. Dicetol was found to produce marked pharmacodynamic effects in experimental animals. Various aspects of this problem are presented in this paper.
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  • B.N. DHAWAN, G.B. MATHUR, V.S. RAJVANSHI
    1968 Volume 18 Issue 4 Pages 445-453
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    Many drugs acting on the central nervous system, like, tranquillizers, and barbiturates are amongst the agents used in thromboembolic discorders and before, during or after surgery. In these patients an alteration in the coagulability of blood has a considerable significance. Very little is known, however, regarding the effect of most of these drugs on coagulation, except for occasional clinical reports (1, 2) of haemorrhagic or thrombotic complications in course of therapy. A study of the effect of these drugs on coagulation has, therefore, been under-taken and the results obtained with 25 drugs are being reported here. A preliminary report of part of this work has been published (3).
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  • TAKASHI BAN, MASAKAZU HOJO
    1968 Volume 18 Issue 4 Pages 454-470
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    Orphenadrine has been reported to improve effectively a variety of skeletal muscle spasms (1-5) and various disorders of parkinsonism (6-9). Orphenadrine is known to be one of anticholinergic agents with weak antihistamine activity (9). The anticholinergic and antihistamine mechanisms seem to be somewhat essential for the antiparkinson drugs (10, 11). The blocking effects of the anticholinergic antiparkinson agents on the reticular ascending function (12) as well as the suppressing effects on the tremor induced either by destructive lesions in the midbrain tegmentum (12) and the reticular formation (14) or by electrical stimulation of these structures (15, 16) indicate that the cholinergic mechanism is involved somewhere in the polysynaptic chains of the ascending and descending pathways from the midbrain. These evidences indicate that the suppression of the arousal response in the cortical EEG is predictive for the prevention of the tremor manifestation in the parkinson patients. Such an effect has been utilized for the evaluation of the antiparkinson agents (10, 12). In the present experiments the effects of various agents including orphenadrine were observed on the arousal responses of the cortical EEG and on the motor responses such as the head turning and neck tremor caused by electrical stimulation of the midbrain tegmentum. However, the uniform and parallel depression of both parameters was not always obtained, varying considerably in effect according to the administered doses and also to the time-length after the administration. The antiparkinson characteristics of orphenadrine were discussed, based on the evidences obtained.
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  • HEITAROH IWATA, ITARU YAMAMOTO, MAKOTO OKA
    1968 Volume 18 Issue 4 Pages 471-481
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    Diazonium compounds have been employed extensively to modify proteins (1-6), to study the composition and structure of enzymes and their relationships to enzyme activity (7-10), and also to produce specific antigenic determinants (11). However, these compounds have restricted interest in their use because of their lack of specificity in formation of different azo derivatives of amino acids, and because of the difficulty of obtaining them in crystalline form. Only a few investigations have been reported on pharmacological activities of diazonium compounds (12-18). During our studies on the antitumor and antibacterial activities of 4(or 5)-aminoimidazole-5(or 4)-carboxamide (a precursor of purine nucleotides) derivatives (12-14), the diazonium compound, 4(or 5)-diazoimidazole-5(or 4)-carboxamide (Diazo-ICA) was found to act as a central depressant in experimental animals (16, 17). It was reported that the diazonium group of Diazo-ICA played an important role in these biological activities (12-14, 16-17). Therefore, it was of interest to obtain detailed information on the pharmacological properties of Diazo-ICA. The present paper reports positive ino- and chronotropic effects of Diazo-ICA on isolated guinea pig atrium caused by its interaction with certain sulfhydryl groups in the tissues. It was also found that these effects of the diazonium compound on the isolated atria seemed to be partially mediated by release of catecholamine from the tissues.
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  • RYUICHI KATO, AKIRA TAKANAKA, MICHIKO TAKAYANAGI
    1968 Volume 18 Issue 4 Pages 482-489
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    The main pathway of drug inactivation occurs in liver microsomes by mixed function oxygenation in the presence of NADPH and oxygen (1). The participation in these reactions of a carbon monoxide-binding hemoprotein called P-450 as the oxygen activating component has been established (1-6). One of characteristics of the drug-oxidizing enzymes of liver microsomes is to have marked sex difference in the activity of rats (7-12). In previous paper, we reported that the magnitude of the sex difference in the drug-oxidizing activity in rats was markedly different according to the substrate used (11, 12). On the other hand, it has been observed that there are no clear sex difference in the activities of microsomal drug-oxidizing enzymes of other species of animals (8, 13). More recently, it was observed in our laboratory that the activity of microsomal NADPH-linked electron transport system, such as, the activity of NADPH oxidase, NADPH-cytochrome c reductase and NADPH-neotetrazolium reductase and the content of P-450 were higher in male rats than in female rats (14, 15). Therefore, it is of interest to establish the relationship between the activities of microsomal NADPH-linked electron transport system and drug-oxidizing enzymes in connection with the sex difference and to investigate whether the such sex difference in the activity of microsomal NADPH- or NADH-linked electron transport system is observed in other species of animals.
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  • KOKI SHIMOJI, HARUKA ASARI, KIKUO NIOH, TAKESHI KAWAMOTO, HIROSHI TAKE ...
    1968 Volume 18 Issue 4 Pages 490-499
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    It is well known that all anesthetics in clinical use more or less have an action of muscle relaxation. As previously reported (1), spontaneous activities of human respiratory muscles decrease as anesthesia is deepened and finally disappear except for the activity of the diaphragm. Spontaneous activities of muscles are, however, the final reflection of various mechanisms by which each anesthetic acts on the central and peripheral nervous systems. Therefore, it is assumed that there are differences in sites and in potency of action on each synaptic level due to the specific characteristics of each anesthetic with regard to muscle relaxation. As for neuromuscular transmission, several authors reported the depressant action of anesthetic gases (2); and others (3-5) described their effects on spinal reflexes. In the above reports, however, the action of the anesthetics was focused upon only one phenomenon, namely neuromuscular transmission or spinal reflexes. In the present study on the cat the differential effects of anesthetics on neuromuscular transmission, the gamma motor system, spinal reflexes and the pathway from the central nervous system to muscle were examined simultaneously in order to detect differences in their sites and potency of action.
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  • NORIMOTO URAKAWA, MIYOSHI IKEDA, YUKIO SAITO, YUTAKA SAKAI
    1968 Volume 18 Issue 4 Pages 500-508
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    In smooth muscle of guinea pig taenia coli, showing spontaneous activity, the curves of rhythmic changes in muscle tension appears parallel to the curves of changes in Po2 level in the medium (1-3). On the other hand, Saito et al. (3) reported that an application of high K (isotonically, 40 mM) caused an increase in oxygen consumption accompanying increase in tension change in taenia coli, and that this was in accordance with the concept (4, 5) that the K-induced tonic response resulted from a transmembrane transport of Ca that depended on the aerobic breakdown of carbohydrates. In the present paper, effects of Ca depletion on the oxygen consumption accompanying muscle tension change both spontaneous and that induced by high K were studied, and a dissociation of the changes in oxygen consumption and muscle tension change was attempted by substituting strontium (Sr) for Ca in the external medium. Some of the results have already been reported (6, 7).
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  • SATISH ARORA, P.K. LAHIRI
    1968 Volume 18 Issue 4 Pages 509-513
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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    Imipramine, a potent antidepressive drug has been shown to antagonize the actions of a number of autopharmacological substances like histamine, 5-hydroxytryptamine, bradykinin, catecholamines and acetylcholine (1). Sigg and his coworkers (2, 3) observed a dual effect of imipramine on the various manifestations of the autonomic nervous system; a blocking action at higher dosage and a stimulant effect with low concentrations. The purpose of the present study was to investigate in more details the interactions between imipramine and acetylcholine at various sites, where acetylcholine is the neurotransmitter. This was done both at the muscarinic and nicotinic site.
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  • RYUICHI KATO, KINICHI ONODA, YOSHIHITO OMORI
    1968 Volume 18 Issue 4 Pages 514-515
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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  • RYUICHI KATO, AKIRA TAKANAKA, KINICHI ONODA
    1968 Volume 18 Issue 4 Pages 516-517
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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  • YOSHIMICHI MURAYAMA, AKIYOSHI SUZUKI, MASAO TADOKORO, FUMINORI SAKAI
    1968 Volume 18 Issue 4 Pages 518-519
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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  • J.N. SINHA, G.P. GUPTA, K.N. DHAWAN
    1968 Volume 18 Issue 4 Pages 519-521
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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  • J.N. SINHA, B.P. JAJU, R.C. SRIVASTAVA, S.S. PARMAR
    1968 Volume 18 Issue 4 Pages 522-523
    Published: December 01, 1968
    Released on J-STAGE: February 02, 2007
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