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Volume 76, Issue 6
Displaying 1-11 of 11 articles from this issue
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Yasuyuki NOMURA1980 Volume 76 Issue 6 Pages 413-427
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSThe ontogenesis of the synaptic function was investigated in the central noradrenaline (NA), dopamine (DA), serotonin (5-HT), acetylcholine (ACh) and GABA nervous systems of developing rats. Monoamines histochemically first appeared on days 12 to 14 in the fetal brain and may exert a trophic action on target neurons as a “differentiation signal”. The presynaptic functions such as the high affinity uptake and depolarization-induced, Ca2+-dependent release of L-[3H]NA, [3H]DA, and [3H]5-HT were observed in synaptosomes and slices from the fetus (18 days of gestation) and brain of newborn rats. Monoamine-stimulated activity of adenylate cyclase and specific binding of ligands in NA(α1, α2, β1, β2), DA, 5-HT, ACh (muscarinic and nicotinic) and GABA receptors indicated dynamic changes through postnatal development. Behavioral findings suggest when neurotransmitter receptors become sensitive and reach functional maturity (NA and DA, already at birth ; 5-HT and muscarinic ACh, 15 ?? 20 days ; GABA, 12 ?? 13 days (mouse)). In addition, differences in behavioral responsiveness to drugs were observed in rats at various developing stages, probably due to the interaction between plural neuronal systems. Finally, the brain undergoing rapid differentiation seems to be most sensitive to hormones and centrally acting drugs. Thus, permanent alteration in central functions may occur when some classes of drugs, dose-dependently, are administrated to animals at the perinatal stage.View full abstractDownload PDF (21959K) -
Yasushi SAKAI, Hiroshi KOGO, Yoshio AIZAWA1980 Volume 76 Issue 6 Pages 429-434
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSEstrogen effects on fatty acid (FA) composition in rat uterine lipids after ovariectomy were investigated. FAs in uterine lipids increased after estrogen injection. Estrogen enhanced the level of FA in phosphatidylethanolamine. The moities of palmitic, palmitoleic, oleic and linoleic acids increased transiently more than twofold, 6 hours after estrogen administration and stearic and arachidonic acids increased to about two-fold 48 hours after this injection. Each FA measured increased 1.7 ?? 2.4 fold in phosphatidylcholine and total lipid, 48 hours after estrogen injection. Therefore, estrogen increases the production of phospholipids and has a considerable influence on the pattern of FA content in phosphatidylethanolamine. Membrane conformation in uterine cells is thus affected.View full abstractDownload PDF (6826K) -
Influences of various antidotes on chemically induced methemoglobinemia and sulfhemoglobinemiaAkira NOMURA1980 Volume 76 Issue 6 Pages 435-446
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSThe influences of methylene blue (MB), thionine, ascorbic acid (ASA), sodium thiosulfate (STS), N-(2-mercaptopropionyl)-glycine (MPG) and reduced glutathione (GSH) on methemoglobin-(MHb)-emia and sulfhemoglobin (SHb)-emia induced by 4-chloroaniline (4-Cl-A) i.p. were studied. Preventive or therapeutic effect on MHb-emia and preventive effect on SHb-emia in mice: MHb formation was inhibited by MB i.p. whether it was administered simultaneously with or after 4-Cl-A, but SHb formation was increased. Similar effects were seen with thionine. Both compounds proved to have MHb and SHb forming activities. STS or MPG, if administered i. p. simultaneously with 4-Cl-A, inhibited formation of MHb, but exerted no effect on delayed SHb formation. However, if administered i.p. or i.v. 120 minutes after 4-Cl-A when the peak of MHb formation had passed, there was a preventive effect on delayed SHb formation. GSH inhibited MHb formation and prevented SHb formation only when it was administered i.v. 120 minutes after 4-Cl-A. ASA did not inhibit MHb formation when it was administered either i.p. or i.v., but showed a preventive effect on SHb formation, if administered 120 minutes after 4-Cl-A. Combined i.v. administration of the corresponding doses to the clinical ones of MB and ASA 120 minutes after 4-Cl-A showed a therapeutic effect on MHb-emia and a preventive effect on SHb-emia. However, at higher dose levels, MB masked the preventive effect of ASA on SHb-emia. Therapeutic effect on SHb-emia in mice and rats: None of MB, STS, GSH and ASA proved to have any therapeutic effects for established SHb-emia. On the basis of these results, significance of clinical usage of drugs in the treatment of chemically induced MHb-emia and SHb-emia is discussed.View full abstractDownload PDF (11987K) -
Takayuki SUKAMOTO, Kunihiko AIKAWA, Keizo ITOH, Takashi NOSE1980 Volume 76 Issue 6 Pages 447-468
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSKB-509, a new derivative of benzodiazepines, increased locomotor activities of mice in doses of 8-32 mg/kg (p.o.) and a decrease occurred with higher doses. This drug was 3-6 and 1-2 times more potent than diazepam (DZP) and nitrazepam (NZP), respectively, in anticonvalsant (anti-pentylenetetrazol, bemegride, strychnine) activities, antiaggressive activity and potentiation of chlorprothixene-induced hypnosis in mice. On the other hand, KB-509 possessed similar potency to DZP and NZP in muscle relaxant activity in mice and inhibition of flexor reflex in cats, and was markedly weaker than DZP and NZP in causing a loss of righting reflex in mice. In the spontaneous EEG activity, KB-509 induced a drowsy pattern and slightly inhibited arousal response of EEG in rabbits, as did DZP. In particular, KB-509 was more potent than DZP in suppressing the amygdala afterdischarge and had a longer duration of action. KB-509 and DZP slightly depressed body temperature, the cardio-respiratory system and the gastrointestinal tract in high doses. Potentiation of spontaneous motility of the uterus and increase of urine excretion were also observed with high doses. In conclusion, KB-509 is superior to both DZP and NZP in the ratio of anticonvulsant and/or taming activities and muscle relaxant activity, and has a weak central depressant activity.View full abstractDownload PDF (23095K) -
Haruo OHNISHI, Chihiro ITO, Kazuo SUZUKI, Takeshi NIHO, Yoshinori IMAI ...1980 Volume 76 Issue 6 Pages 469-477
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSEffects of 5-methyl-7-diethylamino-s-triazolo-(1, 5-a) pyrimidine (trapidil, Rocornal®), a therapeutic agent for ischemic heart disease, on various types of experimental hyperlipemias were studied. With administration of trapidil, elevation of serum high density lipoprotein cholesterol (HDL-C) levels and reduction in serum total cholesterol (TC), low density lipoprotein and very low density lipoprotein cholesterol (LDL-C) and the ratio of HDL-C to LDL-C (LDL-C/HDL-C) were observed in most disease models. Changes in HDL-C levels and LDL-C/HDL-C in the hyperlipemia induced by lipid-enriched diet in mice and in the hyperlipemia induced by high cholesterol diet in Japanese quails were of statistical significance. Also, amelioration of reduction in HDL-C induced by high fat emulsion plus 6-n-propyl-2-thiouracil in rats was observed to be significant. Moreover, trapidil significantly reduced TC, LDL-C levels and LDL-C/HDL-C in the hyperlipemia in hamsters. To investigate possible mechanisms of therapeutic effects of trapidil, blood enzyme activities in Japanese quails with hyperlipemia were assayed. Trapidil showed increases in plasma lipoprotein lipase and serum lecithin-cholesterol acyltransferase activities. These results suggest that trapidil may be an effective chemotherapeutic agent for treating ischemic heart disease.View full abstractDownload PDF (12656K) -
Yutaka SAKAI, Yoshiki MATSUI1980 Volume 76 Issue 6 Pages 479-493
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSA new antidepressant, mianserin (GB-94, Organon), and other known antidepressants, imipramine (IMP), desipramine (DPM), chlorimipramine (CIP), amitriptyline (ATP) and nortriptyline (NTP) were orally administered to respective groups of 25 mice for 3 consecutive weeks, and changes in monoamine metabolisms in the brain were investigated, neurochemically. On the basis of significant difference from the control group, mianserin 20 mg/kg and DPM 20 mg/kg produced no change of the brain contents of DA and 5-HT; IMP 50 mg/kg and CIP 40 mg/kg did not alter NA and DA values, but did decrease 5-HT levels; ATP 30 mg/kg increased only the amount of NA, left unchanged the DA and 5-HT levels, and NTP 20 mg/kg raised the levels of DA and 5-HT, but had no effect on NA. Mianserin, IMP and DPM all facilitated the decrease of both NE and DA as induced by pre-administration of α-methyltyrosine, the substance known to reduce the level of catechlolamines. Both NTP and CTP showed no notable effect. ATP suppressed the reduction of the DA level. Accumulation of 5-HIAA induced 1 hour after treatment with probenecid 250 mg/kg was enhanced by mianserin 20 mg/kg, NTP 20 mg/kg and IMP 25 mg/kg, but was not significantly affected by CIP, DPM and ATP. These results suggest that mianserin activated both the NE and 5-HT metabolic systems, IMP activated the NE system in general, but activated the 5-HT system only at low doses and tended to suppress the formation of 5-HT, in high doses; CIP had no effect on the NE system and suppressed 5-HT, while NTP had no effect on the NE system and tended to activate the 5-HT system, in high doses. The arousal response of hippocampal EEG in the chronic EEG of the rabbit, induced by physostigmine 0.05 mg/kg, i.v., was suppressed by IMP, ATP and CIP, while DPM and NTP were uneffected. Mianserin, rather maintained and prolonged the arousal reaction. Observations made on arousal and sleep phases in long time recording of chronic spontaneous EEG in the rat showed a dose-dependent shortening of the para-sleep phase by mianserin in doses over 30 mg/kg and IMP in doses over 5 mg/kg. ATP 15 mg/kg showed a tendency to shorten the parasleep. Hippocampal and cerebral cortical EEGs at arousal and slow wave stages were analyzed using a signal processor. The power spectra thus obtained showed no significant difference between the effects of mianserin and IMP.View full abstractDownload PDF (18103K) -
Haruo OHNISHI, Hiroshi KOSUZUME, Kazuo YAMAGUCHI, Masami SATO, Sadaomi ...1980 Volume 76 Issue 6 Pages 495-503
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSEffects of trapidil and other coronary vasodilators on retrograde blood flow in acute coronary-ligated dogs, isolated large and small coronary arteries of pig, platelet aggregation, biosynthesis of prostacyclin in isolated aortic rings and hyperlipemia in quails were investigated. Trapidil showed an increase in retrograde blood flow while dipyridamole, nifedipine, diltiazem and dilazep did not. Trapidil and nitroglycerin relaxed large-coronary arteries, while dipyridamole, diltiazem, dilazep and adenosine relaxed small arteries. Trapidil, dipyridamole, diltiazem and aspirin protected against the secondary phase of ADP-induced platelet aggregation in guinea-pig platelet rich plasma more effectively than did nifedipine and dilazep. Trapidil and aspirin protected only against rabbit platelet aggregation as induced by arachidonic acid. Moreover, only trapidil protected against platelet aggregation as induced by prostaglandin G2-thromboxane A2 mixture. Trapidil and dipyridamole enhanced the platelet aggregation protection of prostacyclin. Trapidil also facilitated biosynthesis of prostacyclin more markedly than did the other drugs. Trapidil increased serum content of HDL cholesterol and significantly lowered serum content of triglyceride and the ratio of LDL cholesterol to HDL cholesterol in hyperlipemic quails. Dipyridamole, diltiazem, nifedipine and dilazep, however, showed little effect.View full abstractDownload PDF (11467K) -
Takashi IZUMI, Taiichi NISHIMURA, Kenji SAKAI, Yasushi ABIKO, Yuichi H ...1980 Volume 76 Issue 6 Pages 505-513
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSEffects of atenolol on the cardiovascular system were studied in rats and dogs. Atenolol (10 μg/kg - 3 mg/kg) did not increase heart rate significantly in rats pretreated with reserpine (5 mg/kg), while a significant increase occurred with practolol (30 μg/kg - 3 mg/kg). Atenolol (100 μg/kg) inhibited the response of canine heart (heart rate and myocardial contractile force) to isoproterenol to a similar degree as seen with propranolol (100 μg/kg) did. The ability of atenolol to inhibit vasodilating action of isoproterenol, however, was about 1/12 of that of propranolol. Atenolol (0.5 mg/kg) did not inhibit hemodynamic responses to ouabain and CaCl2 in dogs, while this drug inhibited these responses to isoproterenol. Atenolol decreased heart rate, myocardial contractile force, left ventricular pressure, and rate of rise of the left ventricular pressure (dp/dt LV max) dose-dependently. Atenolol (1 mg/kg) decreased coronary venous outflow and myocardial oxygen consumption in dogs, but did not alter the myocardium to a more reduced state, as determined by coronary arterial and venous lactate and pyruvate levels. These results confirmed that atenolol is a potent cardioselective β-blocker devoid of intrinsic sympathomimetic action. The results also suggest that atenolol inhibits cardiac function without disturbing the intracellular redox state of the myocardium.View full abstractDownload PDF (9915K) -
Kohzoh INOKUCHI1980 Volume 76 Issue 6 Pages 515-523
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSTo acquire data on the mechanism of central effects of adrenergic β-blockers as antihypertensive agents, experiments were done on spontaneously hypertensive rats (SHR). Each group included 5 animals. Propranolol (5 mg/kg), pindolol (0.3 mg/kg), alprenolol (5 mg/kg) or bupranolol (5 mg/kg) were given subcutaneously to the respective groups, once daily for 7 days, while the control group were given no treatment. All the rats were sacrificed 12 hours after the last injection, and the concentrations of the following materials were measured: noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the brain; NA in the heart muscle; adrenaline and NA in the adrenal glands. As compared with the control group, all rats on the β-blockers showed an increase in NA concentration in the brain. Both pindolol and alprenolol, which have an intrinsic sympathomimetic action (ISA), increased DA concentrations in the brain. Both propranolol and bupranolol, which have no ISA, either decreased DA concentrations or showed no effect. No marked change was seen in 5-HT concentration in the brain and of NA in the heart muscle. Catecholamine concentrations in the adrenal glands showed a tendency toward decrease. These results suggest that the mechanism of antihypertensive effects of β-blockers may be due to depression of the peripheral sympathetic activity, as induced by the central inhibitory effects of β-blockers.View full abstractDownload PDF (9917K) -
Kumeji TAKEUCHI, Norihisa INAZU, Noboru HASEGAWA, Yoko YOSHIDA, Kenji ...1980 Volume 76 Issue 6 Pages 525-531
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSInhibitory action of non-steroidal anti-inflammatory drugs (NSAID) on the synthesis and release of prostaglandin (PG) was studied both in vivo and in vitro. In the experiment with PG synthetase from beef seminal vesicle, the potency of NSAID on the inhibitory action of PGE synthesis was: flurbiprofen>4-(p-chlorophenyl)-2-phenyl-5-thiazoleacetic acid (CH-800)>indomethacin>diclofenac-Na>aspirin. Inflamed synovial tissue, as induced 6 hours after carrageenin injection into the knee joint cavity of rats was used to examine the inhibitory action of NSAID on PGE release from the tissue. Both in vivo and in vitro, CH-800 was the most potent and flurbiprofen and indomethacin were next potent of the five drugs. Effects of NSAID on the excretion of PGE and PG main urinary metabolite (PGMUM) in rat urine were determined. The excretion of urinary PGE was significantly decreased by administration of NSAID. Flurbiprofen and CH-800 had the most potent inhibitory action on the excretion of PGEMUM, but the urinary excretion of PGFMUM was not significantly inhibited by NSAID. Thus, the inhibitory effects of NSAID associated with PG synthesis were generally in proportion to the effect of the drugs with PG synthetase, however, there were differences regarding PG synthesis in inflamed tissue and the urinary excretion of PG metabolites.View full abstractDownload PDF (8116K) -
Toshiharu KAMIOKA, Yutaka SAKAI1980 Volume 76 Issue 6 Pages 533-547
Published: 1980
Released on J-STAGE: March 29, 2007
JOURNAL FREE ACCESSBehavioral pharmacological properties of mianserin (1, 2, 3, 4, 10, 14b-hexahydro-2-methyldibenzol[c, f]pyrazino [1, 2-a]azepine monohydrochloride) were investigated in comparison with imipramine (IMP) and amitriptyline (ATP). Mianserin antagonized reserpine-induced hypothermia but to a much lesser extent than IMP or ATP, and did not block the ptosis evoked by reserpine or tetrabenazine. Amphetamine-induced stereotyped behavior was significantly enhanced by both IMP and ATP, but not by mianserin. Unlike IMP or ATP, haloperidol-induced catalepsy in the rat was not blocked by mianserin. Like IMP or ATP, mianserin did not suppress the convulsions induced by bemegride or strychnine in the mouse, and or emetic action of apomorphine in the dog, while only mianserin did not block the convulsions evoded by electric shocks. Mianserin more strongly potentiated the anesthetic action of thiopental than did IMP. ATP showed strong muscle relaxant action and the impairment of coordinated motor activities both in mice and rats, in the inclinated screen test and rotarod test, while, like IMP, these actions of mianserin were significant only in the rat. Catalepsy was not induced nor was the righting reflex suppressed by mianserin. In the low spinal cat, mianserin did not depress the amplitude of extensor MSR. Moreover, the MSR inhibition induced by conditioning stimulation of ipsilateral cutaneous afferents and the MSR potentiation evoked by conditioning stimulation of contralateral saphenous nerve were unaffected by mianserin. The curious behavior of mice and rats was significantly and dose-dependently suppressed by mianserin, and tended to be suppressed by ATP, while an enhancement was seen with IMP in large doses. Mianserin was the most potent in suppressing the fighting behavior induced by long-term isolation of the mouse, and was the weakest in suppressing electric-stimulation-induced fighting behavior, compared with IMP and ATP. Mianserin showed no significant suppression of the muricide behavior of the olfactory bulbectomized rat, while IMP significantly suppressed it. No significant differences were observed among mianserin, IMP and ATP as to their actions on the conflict behavior and the shuttle-box type conditioned avoidance behavior of the rat. These results indicate that behavioral pharmacological actions of mianserin were not always the same as those of IMP and ATP. Therefore, mianserin may be a new antidepressant with mechanisms of action which differ from that of the usual tricyclic antidepressants.View full abstractDownload PDF (19062K)
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