Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 73, Issue 1
Displaying 1-13 of 13 articles from this issue
  • Kiyoko OKUIZUMI, Hisashi KURIBARA, Haruyoshi OGAWA, Sakutaro TADOKORO
    1977 Volume 73 Issue 1 Pages 1-13
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Five male adult rats were trained for 2 hr-sessions per day on a fixed interval (FI) 1.5 min schedule of food reinforcement under a situation in which water was freely provided. The schedule-induced polydipsia was produced in these conditions after 10-15 sessions. After the stabilization of FI-responses (lever-pressings) and post-pellet licking bursts in a polydipsic state, effects of sucrose and three artificial sweetners (saccharin Na, aspartame and Na cyclamate) were investigated by exchanging water for those solutions. Effects of sodium chloride solutions were also studied. When 0.03-4% sucrose solutions were given, the lickings were enhanced in proportion to the concentrations, while no marked change of the FI-responses was observed. At 16% sucrose solution, the lickings were markedly enhanced in the first 20 min, then strongly inhibited, and simultaneously the FI-responses were decreased throughout the session. When 0.03-0.4% saccharin solutions were presented, the lickings and the total intake of fluid were significantly increased regardless of the concentrations. However, 1.6% saccharin solution was rejected, thus the licking counts lowered. The FI-responses were not affected by any concentration of saccharin. After the presentations of 0.1-0.8% aspartame and 0.03-0.2% cyclamate solutions, neither the licking counts nor the FI-responses changed significantly, but 0.4% cyclamate tended to be rejected. No marked change was observed either in the licking counts or the FI-responses after the provision of hypotonic saline solutions (below 0.8%), but 1.6% solution was rejected. The present results suggest that the sense of taste to artificial sweetners is clearly different between rat and man. These findings contribute to the data on pharmacotoxicological factors of artificial sweetners.
    Download PDF (5350K)
  • Tohru SHOJI, Shinobu SAKURADA, Kensuke KISARA
    1977 Volume 73 Issue 1 Pages 15-23
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Metaraminol (MA) (40, 80 and 160μg) was injected i.c. into mice and spontaneous motor activity (SMA) measured by photo-cell counters method was found to increase 30 min after the injection. Ninety min after, the SMA was restored to the saline treated control. MA (80 μg i.c.) was also injected into isocarboxazide (Iso) pretreated mice and the SMA markdly increased as compared with the Iso+saline treated group or tween+MA treated group. When MA was injected i.e. into α-methyl-p-tyrosine (α-MT) pretreated mice, the SMA significantly increased as compared with that of the α-MT+saline treated group, but there was a decrease as compared with that of the tween+saline or tween+MA treated group. In α-MT treated mice. L-Dopa restored the hyper-motor activity of animals treated with MA. Diethyldithiocarbamate (700mg/kg i.p.) had no influence, whereas haloperidol markedly blocked the hyper-motor activity induced by MA. The hyper-motor activity induced by MA in mice raised the question of a possible role of noradrenaline and dopamine in the mediation of this action.
    Download PDF (4287K)
  • Satoshi YAMAMOTO
    1977 Volume 73 Issue 1 Pages 25-36
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    In the present pharmacokinetic studies on beclomethasone dipropionate in rats, it was suggested that most of the beclomethasone-17, 21dipropionate is transformed rapidly into beclomethasone-17-monopropionate or beclomethasone in the blood or tissues and exerts the glucocorticoid effect in the form of beclomethasone. Glucocorticoid activity of beclomethasone was revealed to be 1-10% that of dexamethasone both in the hypothalamopituitaryadrenocortical suppressive effect and liver tyrosine amino transferase inducing effect in rats. Beclomethasone and its propionate derivatives were shown to have higher binding affinity to glucocorticoid receptors in rat liver, thymus and hypophysis than that of dexamethasone. The experimental results herein may serve to explain why beclomethasone and its propionate derivatives showed such a weak glucocorticoid action in comparison with that of dexamethasone. The amounts of receptor-beclomethasone (or its propionate derivatives) complexes which bound specifically to liver nuclei were only 10% or less than those of receptordexamethasone complexes and the in vivo metabolism of beclomethasone and beclomethasone-dipropionate was more rapid than that of dexamethasone.
    Download PDF (5109K)
  • Katsuo WAKABAYASHI
    1977 Volume 73 Issue 1 Pages 37-50
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    The water-soluble contrast medium, N-methylglucamine iothalamate (NMGI), when injected in a dose of 1 ml into the cerebral parenchyma space of dogs (Feldberg's method), diffused within the lateral ventricle at a constant rate of flow against the nerve fibers running therein. Such was recorded by X-ray television and 16 mm cinecamera. Injection of the same dose into the subarachnoid space, however, did not produce these phenomena. Differences in the mode of transfer from brain to heart as the result of three different sites of application (ventricle, parenchyma and subarachnoid space) were investigated using 131I labeled NMGI, the determination of radioactivity being made by two scintillation detectors situated at the head and the heart. The determination of RI activity revealed that the above mentioned three areas of brain have their own characteristic pattern of attenuation from brain to heart, particularly in the case of subarachnoid application. Clonic convulsions after intracranial administration of NMGI in dogs occurred when NMGI was given into the parenchyma but not when given into the ventricle.
    Download PDF (7911K)
  • Masafumi KOBAYASHI, Kohji KAWAMURA, Yasuhito GOTOH, Hisashi SANO, Kiyo ...
    1977 Volume 73 Issue 1 Pages 51-61
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Such effects were studied in male albino mice maintained under isolation circumstances for 7 weeks in order to induce aggressiveness. L-DOPA (25 mg/kg) was given concomitantly with DDC (75 mg/kg) or reserpine (0.1 mg/kg), or each was administered singly and intraperitoneally to subjects twice weekly. Two peaks on the aggressive degree were observed at the 3rd-4th and 6th weeks, respectively. At the first peak, mice treated with L-DOPA and/or reserpine demonstrated aggressive behavior to a higher degree than control mice but at the second peak, to a lower degree. Mice treated with L-DOPA and DDC showed the highest degree at the second peak. Tyramine uptake in the brain measured at the 6th week was enhanced in mice treated with combinations of L-DOPA with reserpine or DDC. Noradrenaline content in the brain was lowered in mice treated with L-DOPA and/or reserpine, in comparison with each control value. It is thus concluded that catecholamine-related drugs influence the degree of enhancement of aggressiveness in modes which vary depending on the form of action of each drug.
    Download PDF (5037K)
  • Minoru YOSHIDA, Akira NISHIO, Seizaburo KANOH
    1977 Volume 73 Issue 1 Pages 63-71
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Leucocytic pyrogen (LP) which is recognized as a mediator of fever reaction induced with bacterial pyrogen could be obtained from the supernatant of the incubation of polymorphonuclear leucocytes (PMNL). On the other hand, many biological active substances could be also obtained from PMNL and such may play an important role in the inflammatory reaction as well as fever reaction. Vascular permeability increasing factor is one of the active substances from PMNL. We have studied the release of Permeability factor (PF) from the incubation of PMNL and some experimental conditions. The following results were obtained; 1) Both PF and LP could be obtained from the crude LP, supernatant of the incubation of PMNL in vitro. 2) PF-3 which expressed as the activity of PF could be detected from 104 cells/ml of PMNL incubation, and FI-3 expressed as the activity of LP could be detected from the incubation of 106 cells/ml of PMNL. 3) FI-3 was more easily inactivated by heating at 56°C-30 min than PF-3. 4) By column chromatography (Biogel P-150) of crude LP, two protein peaks could be detected; in FI-3, the former was stronger than the latter, but in PF-3, the reverse applied. 5) Specific activities of both FI-3 and PF-3 which were divided by protein concentration of their fractions were located in 6.7 × 104 and 1.25 × 104 of the molecular weight of the chromatography as referenced by bovine albumin (M. W. 6.7 × 104) or horse heart cytochrome C (M. W. 1.25 × 104). 6) Activity of PF was not inhibited by pretreatment of cyproheptidine, both an antihistamic and antiserotonic drug.
    Download PDF (4153K)
  • Haruo SAITO
    1977 Volume 73 Issue 1 Pages 73-82
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Mechanisms of the reversal of blood pressure by d-ephedrine (d-EPH) after the administration of l-ephedrine (l-EPH) in rats anesthetized with urethane were investigated. The dose which elicited the reversal was more than 2 mg/kg of l-EPH and more than 1 mg/kg of d-EPH to each injection of d and 1:EPH (10mg/kg i.v.). The reversal was observed up to 60 min after the injection of l-EPH in both male and female cats and dogs anesthetized with pentobarbital-Na. This reversal was not blocked by atropine (1 mg/kg i.v.), hexamethonium (10mg/kg i.v.), diphenhydramine (2mg/kg i.v.), vagotomy and hypotension by blood letting but was blocked by phenoxybenzamine (2.5 mg/kg i.v.). l-EPH inhibited more remarkably a-action of tyramine and epinephrine than d-EPH. In isolated blood vessels of guinea pig and dog, contraction was produced by both l- and dl-EPH at a dose of 1.3 × 10-4 ?? 5 × 10-3 M but d-EPH did not produce contraction. In the isolated dog femoral arterial strips, d-EPH (5 × 10-3 M) inhibited more remarkably the contraction produced by Adr (1.3 × 10-5 M) than l-EPH. Femoral blood flow in dog was increased by the injection of d-EPH (1mg/kg i.v.) after the injection of 1-EPH (1 mg/kg i.v.) rather than before the injection of l-EPH. The reversal is considered to be an indirect action of d-EPH since it disappeared in reserpinized rats, and, also to be an action of a liberating substance other than β-action of CA since it was not blocked by β-blocker. It is suggested that this liberating substance may be 5-HT and that the vasodilating action of d-EPH may to some extent participate in the fall of blood pressure.
    Download PDF (4254K)
  • Haruo SAITO
    1977 Volume 73 Issue 1 Pages 83-92
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    In rats anesthetized with urethane, the reversal of blood pressure by l-isomer (10 mg/kg i.v.) after injection of the l-isomer (10 mg/kg i.v.) disappeared by the pretreatment of phentolamine (5 mg/kg i.v.), phenoxybenzamine (2.5 mg/kg i.v.), chlorpromazine (2.5 mg/kg i.v.), sulpiride (12.5 mg/kg i.v.) and LSD-25 (200 μg/kg i.v.), respectively. The reversal of blood pressure did not disappear with vagotomy and cocaine (10 mg/kg i.v.) and tubocurarine (30 μg/kg i.v.). The reversal was evident in spinal rats and rats administered pchlorphenylalanine (300 mg/kg i.p. for 3 days). The depressor effect of d-isomer was potentiated in rats administered tryptophane (1000 mg/kg p.o. before 4 hr). In rats administered iproniazid (300 mg/kg i.p. before 8 hr) in addition to tryptophane, the decrease in blood pressure was much greater than that seen in the rats treated with tryptophane alone. In rats administered Li2CO3 (2 mEq/kg p.o. twice daily X5), the decrease in blood pressure was increased by twice the value. On the other hand, the level of 5-HT in blood obtained from rat carotid artery was increased with the reversal of blood pressure by d-isomer. Release of 5-HT from rat platelets occurred with incubation (37°C, 20 min) with both d- and l-isomer (3 × 10-3 g/ml). These data indicate that the reversal of blood pressure by d-isomer is due to the effect of 5-HT. Regarding the mechanisms of the reversal of blood pressure, the following results were obtained; 1) The first injection of 1-isomer caused a pressor effect and masked a-action, therefore, the pressor effect of d-isomer disappeared with the second injection. 2) The depressor effect of endogenous 5-HT appeared. 3) Endogeneous 5-HT was released from platelets by the d-isomer. 4) The depressor effect was partially due to dilation of the peripheral blood vessels by the direct and indirect action of the d-isomer.
    Download PDF (4388K)
  • Yumiko OHTAKI, Hitoshi NAKANISHI, Juro UEDA
    1977 Volume 73 Issue 1 Pages 93-102
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    In anesthetized dogs, intrarenal arterial injections of adenosine (Ads) and adenosine 5´ monophosphate (AMP) caused transient, vasoconstrictions, but those of adenosine 5´ diphosphate (ADP) and adenosine 5´ triphosphate (ATP) caused vasodilations. All of these agents produced marked vasodilations in the mesenteric and femoral vascular beds. An i.v. injection of dilazep (10-30 μg/kg) enhanced significantly the effects of Ads and AMP at these three vascular beds, whereas this compound had no effects on results with ADP, ATP, norepinephrine and angiotensin. Administration of theophylline (10-30 mg/kg) given intravenously attenuated Ads and AMP actions, but had no effects on the other four agents. Renal vasoconstrictions induced by Ads, AMP, norepinephrine and angiotensin were followed by slight vasodilations which were abolished by indomethacin (2-5 mg/kg) given intravenously. Based on these findings postocclusive renal vascular responses were examined. The responses were divided into two phases. Phase1 was the initial decrease and phase2 was the successive gradual increase in renal blood flow (RBF). Phase1 was significantly potentiated by dilazep, but inhibited by theophylline. Phase2 was abolished by indomethacin. These results indicate that the postocclusive renal vascular responses may be mediated through Ads and/or AMP and prostaglandin released from the kidney.
    Download PDF (5179K)
  • Hitoshi NAKANISHI, Yumiko OHTAKI, Juro UEDA, Youichi ABE
    1977 Volume 73 Issue 1 Pages 103-112
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    In anesthetized mongrel dogs, the intrarenal arterial (0.2 1.0 unit/kg min) and the intravenous infusion (0.4 ?? 2.0 unit/kg·min) of secretin caused dose-dependent increases of RBF, accompanied by decreases of the calculated afferent arteriolar resistance (Ra) and efferent arteriolar resistance (Re), but produced no significant effect on GFR, urine flow, electrolyte excretion, osmolar clearance and free water reabsorption. The distribution of cortical blood flow was examined using the radioactive microsphere technique. The intrarenal infusion of secretin (1.0 unit/kg·min) increased renal cortical blood flow in the juxtamedullary area much more than in the superficial area, shifting the blood flow from the outer to the inner zone. Simultaneous intrarenal infusion of secretin (1.0 unit/kg·min) and glucagon (0.5 μg/kg·min) produced increases in GFR, urine flow and electrolyte excretion to a lesser degree than those induced by glucagon alone, whereas the increment in RBF and the decreases in Ra and Re were almost to the same degree as those caused by secretin alone. The present results indicate that secretin produces the dilation of afferent and efferent arterioles, resulting in an increase in RBF, with no change in GFR and urine flow, and that the effects of glucagon on renal functions are masked by secretin mainly through the effects on renal hemodynamics.
    Download PDF (5115K)
  • Yutaka MARUYAMA, Tomonori IMAYOSHI, Kazuhiro GOTO, Yukinobu KADOBE
    1977 Volume 73 Issue 1 Pages 113-122
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Interactions of Y-8004 with anti-inflammatory agents were examined in the carrageenin foot edema and adjuvant induced arthritis tests. The combined administration of hydrocortisone with Y-8004 or other acidic non-steroidal anti-inflammatory agents resulted in a synergistic inhibition of edema. The therapeutic effect of a combination of hydrocortisone and Y-8004 was found to be greater than the effect produced by each of the component agents at corresponding doses in the adjuvant induced arthritis test. Y-8004 also maintained the therapeutic effect of prednisolone by alternative administration in succession to prednisolone therapy as well as indomethacin. On the other hand, the combined effect of acetylsalicylic acid with Y-8004 was antagonistic at the combined ratio in 25 to 1, but synergistic at the combined ratio in 100 to 1. Similar results were obtained in combinations of Y-8004 and indomethacin. The acute toxicity of Y-8004 in rats was potentiated by the combined administration of hydrocortisone or acetylsalicylic acid. The toxicity of indomethacin was, however, antagonized by a combined administration with acetylsalicylic acid as well as the anti-inflammatory activity of indomethacin. These results suggest that Y-8004 may make feasible a reduction in dosage or a withdrawal of the steroid prescription. Antagonism between non-steroidal antiinflammatory agents has yet to be established.
    Download PDF (5656K)
  • Hideomi FUKUDA, Yoshihisa KUDO, Hideki ONO, Akifumi TOGARI, Yoshiko TA ...
    1977 Volume 73 Issue 1 Pages 123-134
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Effects of ID-690 on motor systems were compared with those of clonazepam, diazepam and nitrazepam. ID-690 exerted muscle relaxant action in the rotarod method using rats and mice; this action was almost equal in potency to clonazepam and nitrazepam and more potent than diazepam. Pretreatment with ID-690, clonazepam and nitrazepam increased the sleeping time of mice under thiopental anesthesia to the same degree, whereas diazepam produced a lesser effect. ID-690 was almost equal in potency to diazepam and nitrazepam in protecting against oxotremorine-induced tremor in mice, and approximately 10 times as potent as clonazepam. The anticonvulsant action of ID-690 was similar to that of clonazepam. These benzodiazepines effectively augmented the dorsal root reflexes, while showing no effects on the ventral root reflexes. Rigidity in rats due to anemic decerebration was not affected after intraduodenal administration of these drugs, while phasic augmentation of the rigidity by mechanical stimulation of the hind limb was clearly depressed. These drugs had no effects on the neuromuscular junction. From these results, it is concluded that ID-690 has a wider pharmacological spectrum than clonazepam, is almost equal in potency to nitrazepam and is more potent than diazepam.
    Download PDF (5930K)
  • Keisetsu SHIMA, Shinobu SAKURADA, Kensuke KISARA, Hiroshi NAKAHAMA
    1977 Volume 73 Issue 1 Pages 135-142
    Published: 1977
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Nociceptive stimulus was applied to the skin of adult cats by pinching with a serrated forceps or by radiant heat with Pain meter. This stimulation caused motor or emotional responses such as movements of the head and trunk, vocalization, escape and attack. After the administration of pentazocine, these responses disappeared and the animals behaved normally. Analgesic action appeared approximately 15 min after the administration and lasted more than 90 min. Effects of pentazocine on pain-afferent pathways were studied and the evoked potential was recorded by tibial nerve stimulation. Though pentazocine did not influence the evoked potential recorded from somatic sensory area I and mesencephalic central gray, the evoked potential in pre-central association area, nucleus centralis lateralis, nucleus suprageniculatus-limitans and reticularis pontis caudalis was reduced by pentazocine.
    Download PDF (3516K)
feedback
Top