Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 73, Issue 2
Displaying 1-9 of 9 articles from this issue
  • Jun INUI, Yohji MIURA, Hiroshi IMAMURA
    1977 Volume 73 Issue 2 Pages 143-150
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    A system of digital measuring of the cardiac action potential was constructed in order to measure quickly and accurately the resting potential or maximum diastolic potential, overshoot potential, amplitude, time for 50% repolarization and time for 90% repolarization. This system consists of a dual-beam oscilloscope, a digital voltage meter, a digital interval meter and a simple circuit constructed by operational amplifiers. The measurement of the action potential was achieved by tracing only the resting potential or the maximum diastolic potential and the crest of the action potential on the oscilloscope using another beam. The time for measurement was usually 10 ?? 15 sec and errors in measurement were considered to be negligible. This system is considered to be useful for digital measurement of the action potential of various cardiac tissues. This system was applied for observation of effects of bufetolol, an adrenergic β-receptor blocking drug on the action potential of the dog Purkinje fibres. Bufetolol (10-5 M) caused a slight depolarization of the maximum diastolic potential, decreased overshoot potential, amplitude and maximum rate of rise, and shortened the time for 50% repolarization of the action potential. Bufetolol (10-4 M) additionally prolonged the time for 90% repolarization.
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  • Kazuo TAKAHAMA, Takeshi MIYATA, Yoshitoshi KASÉ
    1977 Volume 73 Issue 2 Pages 151-176
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Tranquilizing and other related actions of benzoctamine (Benz), N-methyl-9, 10-ethanoanthracene-9(10 H)-methylamine hydrochloride were studied in comparison with those of chlorpromazine (CPZ) and chlordiaze-poxide (CDP). Toxic symptoms in mice and rats were due to CNS depression. This agent was 4.2 times (s.c.) and 6.1 times (i.p.) as toxic as CDP in mice, 3.8 times (i.p.) more toxic than CDP in rats; 1.9 times, equally and about half as toxic as CPZ, respectively. A potent muscle relaxant action was demonstrated in mice, and a decerebrate rigidity in cats was depressed with Benz. Tonic extension of mice induced by electro-shock was suppressed but chemo-shock was not inhibited. Discriminative and non-discriminative conditioned avoidance responses were depressed in rats. Benz suppressed both fighting behavior in mice and hyperemotionality in rats due to olfactory bulb ablation or long-term isolation; the effects were 1/4 to 1/2 of those of CPZ; 4 to 5 times and 1/2 to 1 time as potent as those of CDP in suppressing effects on fighting behavior and hyperemotionality, respectively. Hyperactivity caused by amphetamine or morphine was reduced, but amphetamine hyperactivity was facilitated in small doses. Benz did not antagonize hypothermia nor ptosis caused by reserpine in rats and apomorphine-induced vomiting was not inhibited in dogs. In small doses, depressing EEG patterns appeared at the limbic system; in large doses, the depression extended to the neocortex and mid-brain reticular formation. EEG arousal response was also depressed. Generally speaking, the effects of Benz on EEG were similar to those of CDP in small doses and those of CPZ in large doses. Thus Benz is a new type of tranquilizer with a potent muscle-relaxant action, and cannot be categorized with major or minor tranquilizers.
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  • Motohide HAYASHI
    1977 Volume 73 Issue 2 Pages 177-191
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Pharmacological effects of ether and water extracts of Shikon, Lithospermum officinale Linne var. erythrorhizon Maximowicz (Borraginaceae) and Tooki, Angelica acutiloba Kitagawa (Umbelliferae) were studied in mice, rats, guinea pigs and rabbits. 1) with an intraperitoneal administration of ether extract of Shikon, writhing symptom, a decrease in locomotor activity in mice and a slight antipyretic effect in rats occurred. Systemic administration of other extracts and oral administration of Shikon ether extract had no significant pharmacological activity on the central nervous system. 2) Water extract of Shikon exhibited a slight inotropic and chronotropic action on isolated atria of guinea pigs and a contraction of isolated ear vessels of rabbits. The cardiovascular responses to Shikon extract were not affected by pretreatment with tolazoline and propranolol. Intravenous administration of Shikon water extract had no effect on blood pressure, but did inhibit respiration in rabbits. On the other hand, Tooki water extract inhibited movement of isolated atria, dilated ear vessels and caused a fall in blood pressure. 3) No extract affected movement of isolated intestine and coagof blood. 4) Oral administration of Shikon extracts revealed anti-inflammatory activity, in particular, ether extract inhibited acute edema and increased vascular permeability, while water extract inhibited proliferation of granulation tissue. Tooki extracts had no effect on inflammatory reaction. 5) Ether extract of Shikon had a local irritative action and oral administration of a large dose resulted in diarrhea in mice. These results suggest that Shikon has anti-inflammatory action and a slight antipyretic effect. Tooki proved to have no significant pharmacological activities.
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  • Motohide HAYASHI
    1977 Volume 73 Issue 2 Pages 193-203
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Pharmacological effects of Shikonin and Acetylshikonin, pigment components of Shikon were studied in mice, rats, guinea pigs and rabbits. The only difference between the chemical structures of the two pigments is that Acetylshikonin has the acetyl radical, while Shikonin does not. Though the activity was slightly different between the two compounds, the pharmacological effect of Shikonin was similar to that of Acetylshikonin. As the two pigments were extracted by ether from Shikon, systemic administration of these pigments showed the same effect as that of ether extract of Shikon as outlined in the first report(1). These compounds had no effect on blood coagulation, but inhibited the anticoagulant effect of heparin in rats. Topical application of both pigments (50mg of 0.1% ointment) inhibited an increased vascular permeability and acute edema induced by histamine, anti-rat rabbit serum and heat. The activity was similar to that of 0.1% phenylbutazone ointment. On the other hand, these pigments increased proliferation of granuloma tissue in the cotton pellet method and promoted wound healing in rats. The results suggest that Shiunko, a main prescription of Shikon, is an effective ointment for cutaneous injuries.
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  • Motohide HAYASHI
    1977 Volume 73 Issue 2 Pages 205-214
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Pharmacological effects of topical application of Shiunko, a main prescription of Shikon (Lithospermum Officinale Linne var. erythrorhizon Maximowicz), were studied in comparison with that of ether extracts of Shikon and Tooki. Ointment of Shikon ether extract (50 mg/site) inhibited markedly an increased vascular permeability and acute edema induced by histamine, serotonin, bromelain, anti-rat rabbit serum and heat. It also inhibited an increase of local cutaneous temperature induced by phlogistic stimulation (ultraviolet irradiation and heat). On the other hand, it accelerated wound healing in rats. The activity of Shikon ether extract on inflammatory reaction was the most potent in 0.2 ?? 0.1% of ointment concentration and was diminished in higher or lower concentrations. Tooki extract inhibited slightly an acute inflammatory reaction, but had no effect on increase of cutaneous temperature and wound healing in rats. Shiunko contains about 0.2% of Shikon and 0.04% of Tooki extract. The effect of Shiunko was similar to that of Shikon ether extract, but the activity was slightly more potent than that of Shikon. Shiunko inhibited rubor, calor and tumor in acute inflammatory reaction and promoted wound healing. Furthermore, it was reported that pigments of Shikon have antibiotic activity. The results suggest that Shiunko is an effective ointment for cutaneous injuries.
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  • Seiichi SATO, Shichiro MARUYAMA, Jiann-Nan CHEN, Hiroichi EBINA, Koyo ...
    1977 Volume 73 Issue 2 Pages 215-228
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Effects of testosterone propionate (TP), 19-nortestosterone (NT) and 4-androstene-3, 17-dione (AD) on the submandibular gland (SMG) of castrated and castrated-adrenalectomized mice were studied by comparing the weight changes of the SMG with those of other androgen sensitive organs, and by quantitative histological and histochemical study of the components in the secretory tubule cells of the SMG. The marked decrease in SMG weight, which was observed following castration, was markedly reversed following administration of TP or NT, but the effect of AD was weak. The decrease in size of the secretory tubule and the decreases of RNA, tryptophan and PAS positive reaction in the secretory tubule cells observed following castration, were markedly reversed following administration of TP and NT, but the effect of AD was weak. In the case of castrated-adrenalectomized mice, changes in SMG weight, secretory tubule size and RNA content in the secretory tubule cells were similar to those observed in castrated mice. The effect of the three steroids on the levator ani muscle weight of castrated-adrenalectomized mice was much the same as the effect on SMG weight. In the prostate, however, no significant weight increases were observed following administration of NT and AD. Remarkable increases in prostate weights were observed only in the case of TP administration. The above results suggest that the hypertrophy of SMG caused by these steroids may be chiefly due to increased secretory components in the secretory tubule cells such as the PAS positive mucin and the tryptophan-containing protein of which the synthesis is provoked by the RNA synthesized with the administration of these steroids. The sensitivity of SMG to these steroids is considerably different from that of accessory genital organs such as the prostate.
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  • Seiji MORITA, Yasuo IRIE, Sachiko SAKURAGI, Hideaki KOHRI, Hiroshi NIS ...
    1977 Volume 73 Issue 2 Pages 229-235
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    The kinetics (absorption, distribution and excretion) of carteolol were investigated after oral and intravenous administration to man, rats, Beagle dogs and rabbits. The half-life of carteolol in plasma was 1.22 ?? 1.45 hr in rats, 1.73 ?? 2.08 hr in dogs and 1.42 ?? 1.43 hr in rabbits, and was independent of the route of administration. The absorption rate constants, obtained from log(C1-C) ?? time plot, after oral administration were 1.89 hr-1 in rats, 1.04 hr-1 in dogs and 1.54 hr-1 in rabbits. There were no differences between tablet and film coated tablet in the pharmacokinetic parameters of carteolol in man after oral 30 mg (tablet or film coated tablet) administration [half life (t1/2)=4.50 hr (tablet), 4.30 hr (film coated tablet), elimination rate constant (k2)= 0.154 hr-1 (tablet), 0.161 hr-1 (film coated tablet)]. The elimination rate constant, obtained from Sigmaminus plot after 2, 5 and 10 mg oral administration, was 0.137 ?? 0.160 hr-1.
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  • Keisetsu SHIMA, Ken ANEZAKI, Shinobu SAKURADA, Kensuke KISARA, Hiroshi ...
    1977 Volume 73 Issue 2 Pages 237-242
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Effects of morphine were studied in 36 gallamine triethiodide immobilized adult cats under light N2O anesthesia. Single units were recorded from the nucleus dorsal raphe using a stainless steel microelectrode. Dorsal raphe neurons were divided into two types; one was a clock-like (CL) neuron which was typically slow in rate, rhythmic and stable throughout recording time, and the other was a non-clock like (NCL) neuron which was relatively irregular in pattern as compared with CL neuron. Out of 36 neurons recorded in this experiment, 13 were CL neurons and 23 were NCL neurons. Mean discharge rates (spikes per sec) of CL neuron and NCL neuron were 2.84 (range of 2.01 ?? 3.68) and 4.11 (range of 0.10 ?? 35.09), respectively. None of the 13 CL neurons responded to the nociceptive (pinch and/or brdaykinin) and non-nociceptive (hair bending and/or tapping) stimuli. On the contrary, out of 23 NCL neurons, 13 responded to both nociceptive and non-nociceptive stimuli, 4 were responsive to only non-nociceptive stimuli and 6 were not responsive to these stimuli. Receptive fields of NCL neurons were wide with various somatic modalities. The latency for bradykinin (3 μg) was 6.46±0.77 sec. Effects of morphine were examined in 6 CL neurons and 12 NCL neurons. After morphine, no nociceptive neuron responded to nociceptive stimuli, although there was no appreciable change in the responsiveness to non-nociceptive stimuli. Firing frequency and pattern of all CL neurons were unaffected after morphine. Out of 12 NCL neurons, 7 were unaffected in firing frequency and 5 were decreased after morphine.
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  • Showa UEKI, Yutaka GOMITA, Yasunori ARAKI, Katsushi YAMADA, Hiroyuki Y ...
    1977 Volume 73 Issue 2 Pages 243-255
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Effects on the central nervous system of ID-690, a new benzodiazepine derivative were investigated and compared mainly with those of diazepam in mice and rats. Locomotor activity of the rat was increased with ID-690, at doses of 2-5 mg/kg p.o., as with diazepam. ID-690 was approximately 5 times more potent than diazepam in inhibiting fighting behavior of long-term isolated mice. Hyperemotionality induced by either septal lesions or olfactory bulbectomy was also inhibited by ID-690. This effect was almost the same in potency as that of diazepam. ID-690 was only 1/30 as potent as diazepam in preventing maximal electroshock convulsion, while it was approximately 18 times more potent than diazepam in suppressing pentetrazol convulsion in mice. ID-690 was approximately 5 times as potent as diazepam in impairing rotarod performance in mice. The muscle relaxant effect of ID-690 was approximately 10 times as potent as diazepam, as measured with an inclined screen test in mice. Thus the effect of ID-690, as compared with diazepam, was characterized by its relatively potent muscle relaxant and extremely potent anti-pentetrazol convulsant action.
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