Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 83, Issue 2
Displaying 1-9 of 9 articles from this issue
  • Norio AKAIKE
    1984 Volume 83 Issue 2 Pages 93-104
    Published: 1984
    Released on J-STAGE: March 07, 2007
    JOURNAL FREE ACCESS
    Cl- current in GABA-sensitive neurons of the frog dorsal root ganglia was separated from other Na+, Ca2+ and K+ currents using the suction pipette technique which allows internal perfusion and current clamp. Adequacy of the internal perfusion technique was assessed from the reversal potential for GABA-induced Cl- current (EGABA) at various intracellular Cl- concentrations. EGABA was equal to the Cl- equilibrium potential (Ec1) and behaved as a simple Cl- electrode following changes of external and internal Cl- concentrations ([Cl]0 and [Cl]1). EGABA changed by 58 mV for a tenfold change in either [Cl]0 or [Cl]i at constant [Cl]0 or [Cl]1, respectively. GABA-induced Cl- conductance increased dose-dependently. In addition, single Cl- channel current (icl) and conductance (γc1) were estimated from the Cl- current fluctuation by using both power spectrum and amplitude histogram methods, and the theoretical values were compared with those measured directly by a conventional inside-out patch clamp technique.
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  • Haruo OHNISHI
    1984 Volume 83 Issue 2 Pages 105-114
    Published: 1984
    Released on J-STAGE: March 07, 2007
    JOURNAL FREE ACCESS
    The effects of intravenous administration of human or mouse pepsin were investigated on Masugi nephritis in rats and mice, which is an experimental model of glomerulonephritis in humans. Injection of anti-kidney serum to rats significantly increased the urinary protein excretion, serum levels of fibrinogen, cholesterol and immune complex, significantly decreased serum immunoglobulin G and complement levels, and caused histopathological changes such as detachment of endothelial cells from basement membrane, thickening of basement membrane, fusion of foot process and increase in hyaline cast in renal tubuli. Deposit of anti-rat IgG on glomerular capillary wall was also observed. All of these changes were ameliorated or showed a tendency to be ameliorated by intravenous administration of human pepsin, and the mechanism responsible for these effects was suggested to be selective decomposition of immune complex. Marked increase in urinary protein excretion was also observed in mice that intravenously received anti-kidney serum. This increase was suppressed by intravenous administration of human or mouse serum, the latter showing a stronger effect.
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  • Shuichi KAI, Hisashi KOHMURA, Katsumi ISHIKAWA, Toshihito KADOTA, Shig ...
    1984 Volume 83 Issue 2 Pages 115-122
    Published: 1984
    Released on J-STAGE: March 07, 2007
    JOURNAL FREE ACCESS
    In the preceding study, neonatal deaths were observed when an analgesic, butorphanol tartrate (BT), was administered subcutaneously to female rats during the perinatal and lactating periods. In the present study, cross-fostering using CRJ:CD (Sprague-Dawley) rats was employed to clarify the cause of death. When the litters naturally delivered from dams receiving BT (25 mg/kg/day, s.c.) during the perinatal period were switched among one another within the BT-treated dams or placed with control (saline-treated) dams, the viability of newborns on postpartum day 3 was significantly lowered. Since some of the BT-treated dams were observed to neglect the delivery cares that were fundamental to dams such as removing amnions, umbilical cords and placentas, as well as gathering and lactating to newborns immediately after natural delivery, it was considered that death after cross-fostering was the result of the pups being emaciated before cross-fostering. This finding was supported by the fact that a significant elevation in the viability was revealed when the newborns Cesarean-delivered from BT-treated dams were placed with control or untreated dams. No significant effects of BT were observed on the viability and body weight of newborns at birth and on those of pups from postpartum day 3 through the weaning day.
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  • Kouzi OHMINAMI, Eiko MATSUOKA, Yukari TAKAHASHI, Hiromichi OKUDA, Dais ...
    1984 Volume 83 Issue 2 Pages 123-132
    Published: 1984
    Released on J-STAGE: March 07, 2007
    JOURNAL FREE ACCESS
    The present experiments were carried out to elucidate the effect of mazindol feeding on obese mice made by goldthioglucose injection. Mazindol was added to the diet at the level of 0.5, 2, 10 mg/kg body weight. It was found that oral administration of mazindol reduced the body weight gain and perimetrial adipose tissue weights increased in GTG-obese mice. Decreased adipose tissue weights were correlated with the decreased level of size and volume of fat cells. Basal lipolytic activity and adrenaline-induced lipolysis were also significantly decreased in mazindol groups as compared to those in GTG-obese mice that were not administered mazindol. These results indicate that the weight reduction induced by mazindol administration might not be due to increase in fat mobilization. The increased level of liver and serum lipid induced by GTG-obcsity was also found to be improved by mazindol. Scanning electron micrographs indicated that the villous width of the small intestine were significantly smaller in the mazindol group that those in the GTG-obese group. Sucrase and esterase activities of the small intestine were also decreased by mazindol feeding as compared to those in the GTG-obese mice. Based on these results, mechanisms of action of mazindol were discussed.
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  • Katsuya NAGAI, Tsutomu MORI, Minoru OOKURA, Hisatoshi TSUJIMOTO, Hachi ...
    1984 Volume 83 Issue 2 Pages 133-145
    Published: 1984
    Released on J-STAGE: March 07, 2007
    JOURNAL FREE ACCESS
    To elucidate the mechanism of the action of mazindol, an anorectic drug, mazindol effects on behaviors of rats such as feeding, drinking and activities were examined. Mazindol (40 mg/100 g of diet) addition to the diet elicited the transient decrease in food and water intakes, and increases in Animex and running wheel activities compared to those behaviors seen before the mazindol addition. The mazindol addition essentially did not affect the circadian rhythms of the above behaviors. Continuous infusion of mazindol (1-10 ng/h) into the brain reduced the total food intake and increased the light period food intake. The strongest effect of mazindol on food intake was observed when it was infused into a site of median eminence which was 2 mm posterior to the suprachiasmatic nucleus of the hypothalamus. This fact suggests that the site of the anorectic action of mazindol might be located in this area. Since food efficiency (=body weight increase per day/food intake per day) reduced during the period of mazindol addition to the diet in the above experiment, metabolic alterations due to mazindol were examined in rats. The results suggest that mazindol administration enhances degradations of proteins and amino acids and increases gluconeogenesis in the liver.
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  • Hisashi KURIBARA, Sakutaro TADOKORO
    1984 Volume 83 Issue 2 Pages 147-158
    Published: 1984
    Released on J-STAGE: March 07, 2007
    JOURNAL FREE ACCESS
    Effects of amantadine on ambulatory activity in mice and conditioned avoidance responses in rats were investigated. In addition, the change in diurnal drinking rhythm induced by free intake of amantadine solution was also examined in mice. Amantadine (10-40 mg/kg, i.p.) tended to increase the ambulatory activity in mice. Pretreatment with amantadine (10-40 mg/kg, i.p.) at 30 minor 4 hr before augmented the ambulation-increasing effect of apomorphine (0.5 mg/kg, s.c.), but attenuated that of methamphetamine (2 mg/kg, s.c.). When amantadine solution of 0.1 mg/ml or 0.4 mg/ml was freely given to mice for 7 or 21 days, the amount of fluid intake per day decreased slightly, and the daily doses of amantadine intake were estimated to be 15-80 mg/kg/day. However, no marked change in the diurnal pattern of drinking, showing a higher rate during the dark period and a lower rate during the light period, was observed. These mice also demonstrated an increased sensitivity to the ambulation-increasing effect of apomorphine and a decreased sensitivity to that of methamphetamine as compared with the control mice that drank water with no added drugs. Amantadine (10-20 mg/kg, i.p.) did not induce a marked change in the avoidance responses in rats. However, more than 40 mg/kg, i.p. of amantadine suppressed the avoidance responses with a general worsening of bodily condition. Amantadine (10-20 mg/kg, i.p.) did not modify the avoidancefacilitating effects of methamphetamine (0.13-1 mg/kg, s.c.), atropine (1.3-10 mg/kg, s.c.) and scopolamine (0.031-0.13 mg/kg, s.c.), but attenuated the avoidance-suppressing effects of chlorpromazine (0.25-2 mg/kg, s.c.), haloperidol (0.018-0.05 mg/kg, s.c.), tetrabenazine (0.25-1 mg/kg, s.c.), pilocarpine (2-8 mg/kg, s.c.) and physostigmine (0.1-0.4 mg/kg, s.c.) in a dose-dependent manner. The present results suggest that amantadine affects not only the central catecholaminergic neurons but also the other neurons.
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  • Takemasa SHIRAISHI
    1984 Volume 83 Issue 2 Pages 159-172
    Published: 1984
    Released on J-STAGE: March 07, 2007
    JOURNAL FREE ACCESS
    The effects of mazindol on the salivary secretion of dogs was investigated. Mazindol (2 mg/kg, i.v.) decreased the volume and pressure of salivary secretion induced by either chemical (carpronium) stimulation or electrical nerve stimulation. It also reduced spontaneous salivary secretion. Secretion velocity in the mazindol treated group was significantly less than in the physiological saline administered control group at 4 to 6 min after injection. Saline and mazindol produced no significance differences in Na+, Cl- or K+ concentrations in the saliva or serum. Thus mazindol inhibition of salivary secretion was not caused by ion transport. The existence of some other inhibitory mechanism is suggested. The effects of mazindol on the peripheral and central control of gastric acid secretion was also investigated in rats. Gastric acid secretion induced by direct application of cholinergic agents on oxyntic cells was not affected by mazindol. Gastric acid secretion induced by insulin and/or 2-DG, on the other hand, was markedly inhibited by intra-hypothalamic injection or systemic (i.v.) injections of mazindol. Electroosmotic mazindol mimicked the effects of glucose in the lateral (inhibition) and ventromedial (excitation) hypothalamus. The results suggest that the inhibitory effects of mazindol on salivary secretion may be through the hypothalamic feeding control centers. Mazindol also directly affected gastric acid secretory neurons in the lateral hypothalamus. It might thus be expected to be effective in the treatment of obesity.
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  • Yoshitoshi KASE, Toshinori HIDAKA, Takeshi MIYATA, Kazuo TAKAHAMA, Yos ...
    1984 Volume 83 Issue 2 Pages 173-181
    Published: 1984
    Released on J-STAGE: March 07, 2007
    JOURNAL FREE ACCESS
    Pharmacological effects of brovanexine hydrochloride (BR-222), a new expectorant, on the respiratory tract system was studied in comparison with that of bromhexine hydrochloride. 1. When doses ranging from 5 to 40 mg/kg of BR-222 were given orally (p.o.) or intraduodenally (i.d.) to rats, rabbits and dogs, it caused a significant increase in the output volume of respiratory tract fluid (RTF). It was almost as potent as bromhexine, but its pattern of increasing RTF was different from that of bromhexine. The increase in the serous ingredient of RTF after BR-222 administration seemed to be more remarkable than that after bromhexine treatment, though both drugs had no influences on the component ratio of glucose or protein in the RTF of dogs. 2. BR-222 at 10 and 20 mg/kg (i.d.) showed a tendency to reduce the viscosity of RTF in anesthetized dogs and so did bromhexine. A dose of 10 mg/kg (i.d.) of BR-222 also showed a tendency to reduce the viscosity of sputum obtained from the SO2-exposed rabbits. 3. A dose of 6 mg/kg (i.m.) of BR-222 caused a significant increase in the mucociliary transport rate in unanesthetized pigeons; in contrast with this, bromhexine caused a slight decrease. 4. Both drugs given orally showed no antitussive effects when examined by the “coughing dog” method.
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  • Kanichi NAKAMURA, Akihiko NAKAGAWA, Minoru TANAKA, Hiroshi MASUDA, Yas ...
    1984 Volume 83 Issue 2 Pages 183-191
    Published: 1984
    Released on J-STAGE: March 07, 2007
    JOURNAL FREE ACCESS
    Disulfiram-like reactions have been reported in patients receiving cephem antibiotics which possess a mercaptomethyltetrazole (Me-TZ) side chain in their molecular structure. The present study focused on the elucidation of the relationship between the formation of Me-TZ and its inhibitory action on alcohol metabolism after treatment with the cephem antibiotics. The cumulative urinary excretion of Me-TZ was determined in healthy volunteers and laboratory animals after i.v. administration of the cephem antibiotics: cefinetazole (CMZ), cefoperazone (CPZ) and latamoxef (LMOX). In humans, monkeys and rodents, the extent of urinary excretion of Me-TZ was found in the order of CPZ>LMOX>CMZ-treatment. To assess their influences on dehydrogenation of ethanol (EtOH) and acetaldehyde (AcH), rats and monkeys were treated with a single or multiple i.v. dose of Me-TZ and cephem antibiotics prior to the EtOH treatment. The blood EtOH levels were not affected with either the Me-TZ or the cephem pretreatments. On the contrary, the AcH levels were significantly elevated with each of the pretreatments. The dose response curves for AcH levels showed parallel lines corresponding to the urinary excretion of Me-TZ, i.e., CPZ>LMOX>CMZ-treatment. These results suggest that there are some differences in the disulfiram-like reactions among animal species and antibiotics, which will be attributed to the intrinsic distribution and stability of each of the antibiotics in the body.
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