Enzymic coupling of catharanthine and vindoline to form 3',4'-anhydrovinblastine by horseradish peroxidase.
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Antineoplastic Agents, Phytogenic↗
Biomedical subjects
M Misawa
Publications and source records attributed to M Misawa.
Effects of antiallergic drugs on bronchial and cutaneous anaphylaxis in Lewis rats.
Effects of antiallergic agents on 2,4-dinitrophenylated Ascaris extract (DNP-As)-induced bronchial asthma were studied in Lewis rats, and compared with those on passive cutaneous anaphylaxis (PCA). Effects of methysergide and chlorpheniramine on the bronchial asthma model were also investigated. Rats were actively sensitized with DNP-As antigen and with killed Bordetella pertussis. After 8 d, asthmatic response was provoked by inhalation of DNP-As. The bronchomotor response was measured with a modified Konzett-Rössler method in diaphragm-sectioned rats. The inhalation of DNP-As caused a marked asthmatic bronchoconstriction without significant effect on systemic blood pressure and heart rate. Disodium cromoglycate (DSCG), 10 mg/kg, i.v., trans-4-guanidinomethylcyclohexanecarboxylic acid p-tert-butylphenyl ester hydrochloride (NCO-650) and tranilast at doses of 30 and 100 mg/kg, intraduodenally, significantly inhibited the asthmatic response. Chlorpheniramine and methysergide at a dose of 1 mg/kg, i.v. also significantly inhibited it. The above doses of NCO-650 and tranilast significantly inhibited 48 h PCA, while DSCG almost abolished the PCA. These results indicate that 1) NCO-650 and tranilast inhibited both the asthmatic response and PCA in almost the same degree, 2) DSCG inhibited PCA much more strongly than asthmatic response, and 3) histamine and 5-hydroxytryptamine may be involved in this asthmatic response.
Anaphylaxis↗
[Effects of flutropium bromide, a new antiasthma drug, on mediator release from mast cells and actions of mediators].
The effects of flutropium bromide (Ba598Br), a new antiasthma drug possessing the quarternary ammonium structure of atropine derivatives, on mediator release from mast cells and on actions of leukotriene (LT) D4 and serotonin were investigated. Flutropium bromide (3 and 10 mg/kg, i.v.) showed an inhibitory action on the 48 hr homologous PCA in guinea pigs. Atropine showed no inhibitory effect. Flutropium bromide also inhibited the release of histamine from isolated rat mast cells stimulated by antigen, although the inhibitory action was weaker than that of disodium cromoglycate. Atropine also had no inhibitory action in this case. Flutropium bromide and atropine showed no antagonistic action against LTD4-induced contraction of isolated tracheal smooth muscle of guinea pigs. Inhalation of flutropium bromide (0.3%) also showed no antagonistic action against serotonin-induced bronchoconstriction in dogs. From the above results, it is indicated that flutropium bromide has a weak mast cell stabilizing action, but no antagonistic action against LTD4 and serotonin.
Animals↗
[In vitro evaluation of mucolytic activities of some expectorants using porcine gastric mucin].
The measurement of viscoelasticity of airway secretions (sputum) has been very difficult, because the secretions, mainly consisting of high molecular weight glycoproteins, are heterogeneous and non-Newtonian viscous fluid. In the present study, a new in vitro method was devised for evaluating the effects of mucolytic expectorants, using porcine gastric mucin as a mucous fluid. Twenty percent porcine gastric mucin solution was prepared by dissolving it in tris-HCl buffer solution. The mucolytics tested were incubated with the mucin solution at pH 7.0 and 37 degrees C for 30 min. The viscoelasticity of mucous fluid was determined by the glass plate method and rheometer method. The two cysteine-mucolytics, acetylcysteine (10(-3)-10(-1) M) and ethylcysteine++ (10(-3)-10(-1) M) showed a marked viscoelasticity-lowering effect with either method. On the other hand, another cysteine-mucolytic, carbocysteine had no mucolytic effect at pH 7.0, but showed its effect at pH 6.0. A protease-mucolytic, alpha-chymotrypsin (0.1-10 mg/ml), remarkably lowered the viscoelasticity of mucin fluid with either method. Bromhexine (3 X 10(-4)-3 X 10(-3) M) had no mucolytic effect even at the range of pH 6-8. From the above findings, it is indicated that distinct evaluation of the mucolytic actions of expectorants is feasible using porcine gastric mucin. The glass plate method has many advantages over the rheometer method in terms of required sample volume, measurement time, inexpensive, and so on.
Acetylcysteine↗
Cross-physical dependence of several drugs in methaqualone-dependent rats.
We investigated the characteristics of physical dependence on methaqualone. Rats were made physically dependent on methaqualone by the use of the drug-admixed food (DAF) method for 33 days. Pentobarbital, barbital, ethanol and diazepam were cross-administered against methaqualone to evaluate the degree of suppression of methaqualone withdrawal signs as an index for the cross-physical dependence liability of these drugs to methaqualone. To evaluate the cross-physical dependence liability, we used AUC of body weight loss and withdrawal scores between the first cross-administration (9 hr after the withdrawal) and 27 hr after the withdrawal. AUC of weight loss was significantly suppressed by the four test drugs as compared to each control. Withdrawal scores were also significantly inhibited by the cross-administration of barbital, ethanol and diazepam. Considering that the rats given barbital or ethanol fell asleep after the cross-administration, diazepam seems to cause the strongest suppression of methaqualone withdrawal signs among the four test drugs. Thus, physical dependence on methaqualone may be similar by nature to that on benzodiazepines rather than barbiturates and alcohol.
Animals↗
Genetic differences in preferences for morphine and codeine in Lewis and Fischer 344 inbred rat strains.
Preferences for morphine and codeine in two inbred strains of rats, Lewis and Fischer 344 (F344), were systematically investigated using the drug-admixed food (DAF) procedure. Rats were allowed access to food only between 10:00 a.m.-4:00 p.m., but allowed free access to water. The rats were allowed to choose either DAF (0.5 mg/g) or normal food on the first day and then were allowed access only to DAF on the second and third days. After this schedule was repeated 10 times, they were again allowed to choose either DAF or normal food for a successive 8 days. In both strains, preferences for morphine and codeine rapidly increased; the preferences in Lewis rats were significantly higher than those in F344 rats during the daily choice trials. In the range of 0.25 to 1 mg/g for the DAF concentration, there was a negative correlation between the preference and concentration in Lewis and F344 rats, except in the codeine group of F344 rats. When a test dose (60 mg/kg and 30 mg/kg, s.c., in Lewis and F344 rats, respectively) of morphine or codeine was given at 30 min before the beginning of the choice trial, Lewis rats, but not F344 rats, showed a significantly lower preference for the respective drug. The above results indicate that genotype is an important determinant of the degree of preferences for morphine and codeine.
Animals↗
A new rhinitis model using chemical mediators in rats.
No good experimental model for studying rhinitis, has been hitherto available. In the present study, development of a new rhinitis model using chemical mediators was attempted, especially to establish an index of nasal congestion. Male Wistar rats were anesthetized with pentobarbital-Na. Nasal cavities were ventilated between both cannulae inserted into the nasopharynx and bilateral nostrils, with an artificial respirator. Intranasal resistance was recorded with a modification of a Konzett-Rössler apparatus as a change in ventilation overflow (VO). To provoke rhinitis, some mediators were inhaled into the nasal cavities with an ultrasonic nebulizer for 5 min. To assess the capillary permeability of the nasal mucosa, exudation of Evans blue was determined by injecting the dye before inhalations of mediators. Inhalation of histamine (0.01, 0.1, 0.3%), bradykinin (0.01, 0.1%) and ACh (0.3%) markedly increased VO, while inhalation of serotonin (0.01, 0.1, 0.3%) did not increase VO. Histamine, bradykinin and high concentration of ACh significantly increased the dye exudation in the nasal cavities, although serotonin did not. From the above results, it is concluded that 1) a new rhinitis model in which symptoms of nasal blockage and increased capillary permeability in nasal mucosa are quantitatively determined, was established, and 2) histamine- and bradykinin-inhalations can cause rhinitis-like symptoms, although serotonin-inhalation can not.
Airway Resistance↗
Effects of platelet-activating factor on rat airways.
Effects of platelet-activating factor (PAF) on the rat airways were investigated. Male Wistar rats were anesthetized, and PAF was inhaled into the lungs through a tracheal cannula for 5 min using an ultrasonic nebulizer. The bronchomotor response was measured with a modified Konzett-Rössler method in rats immobilized with decamethonium bromide. The inhalation of PAF caused a marked bronchoconstriction, dose-dependently, in a concentration range of 0.0001 to 0.01%. The bronchoconstrictor potency of PAF was about ten times higher than that of ACh. On the other hand, histamine inhalation gave only a slight bronchoconstriction even at the high concentration of 0.1%. The bronchomotor response to PAF was accompanied by a marked, sustained decrease in systemic blood pressure, in a dose-dependent manner. Repeated inhalations of PAF (0.001%) at an interval of 60 min resulted in a pronounced tachyphylaxis in the bronchoconstrictor response, but not in the hypotensive response. Combined inhalations of PAF with ACh or histamine did not produce a potentiation by PAF of the bronchoconstrictor responses to ACh and histamine. These findings show that PAF is a strong bronchoconstrictor agent in rats and that there is no interaction between PAF and other mediators in the acute bronchoconstrictor response.
Acetylcholine↗
[The analects of Hajime Hoshi (no. I)] (Jpn).
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History of Pharmacy↗
Elicitation of bovine antibody to BLV-gp51 by BLV-vaccination.
This study was carried out to demonstrate sequential changes of antibody response to gp51 of BLV in bovine hosts injected with BLV-vaccine. BLV vaccine was prepared from culture fluids from FLK-BLV cells by treatment with 0.1% formalin for 48 hrs at 4 degrees C followed by ultrafiltration and lyophilization. Sterile vaccine containing 300 mg protein/ml, 1 mg of which was reactive by ELISA with monoclonal anti-BLV-glycopeptide up to 1:256 dilution, was injected intradermally with Freund's adjuvant into two 1-month-old Holstein calves seronegative for BLV. The first and second booster injections were given without adjuvant 3 and 15 weeks, respectively, after the initial injection. Sera collected weekly from these animals were analyzed to monitor development of antibody to BLV-gp51 by Western blotting and immunoferritin electron microscopy, as well as by ELISA to whole BLV and to BLV-gp51 partially purified by column chromatography. Antibody to BLV-gp51 was detected in sera collected 2 weeks after the initial injection, increased 2 weeks after the first booster, maintained its level during the following 10 weeks, and increased again 2 weeks after the second booster injection. Infectious BLV was not detected by syncytium-formation assay of lymphocytes collected 15 weeks after the initial injection. This study demonstrated sequential changes of anti-BLV-gp51 antibody elicited in bovine hosts subsequent to injection of formalin-treated BLV. Further analysis of bovine antibody to BLV-gp51 may help develop improved BLV-vaccine.
Animals↗
[Induction of physical dependence on morphine and genetic analysis of morphine withdrawal signs in mice].
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Animals↗
[The effects of noscapine and chlorpheniramine on physical dependence and antitussive activity of dihydrocodeine].
The effects of noscapine and chlorpheniramine on physical dependence liability and antitussive activity of dihydrocodeine, a narcotic antitussive, were studied. For developing physical dependence, male Sprague-Dawley rats were treated with dihydrocodeine (DC), noscapine (N), and chlorpheniramine (CP) singly or simultaneously admixed with food (drug-admixed food method (DAF): DC: 0.125, N: 0.25, CP: 0.05 mg/g of food, for 7 days) or were intermittently medicated for 3 days at one-hour intervals through an implanted intravenous cannula (infusion method: DC: 0.5-2, N: 1-4, CP: 0.2-0.8 mg/kg x 24 times/day). Subsequently, rats were treated with naloxone (0.5 mg/kg, sc) and checked for withdrawal signs during 3 hours. Naloxone-precipitated body weight loss of DC was suppressed by simultaneous administration of N or CP. In combined group of DC, N, and CP, withdrawal signs, such as body weight loss, body shakes, and diarrhea, were more remarkably suppressed. Papaverine, the same kind of spasmolytic as N, was tested by the same schedule of DAF. Papaverine did not suppress the naloxone-precipitated withdrawal signs of DC. These results suggest that suppressive effect of N is not due to its spasmolytic action. On the other hand, the cough reflex was induced by electric stimulation in guinea pigs and the fifty percent of antitussive dose (AtD50) was estimated in order to evaluate the influence of N and CP on antitussive effect of DC. N and CP did not change the antitussive effect of DC. These results may suggest that N and CP suppress the development of physical dependence of DC without diminishing the pharmacological effects of DC.
Animals↗
[Effects of platelet activating factor on the bronchial musculature and vasculature in dogs].
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Animals↗
Increased synthesis of ajmalicine and catharanthine by cell suspension cultures of Catharanthus roseus in response to fungal culture-filtrates.
The ammonium sulfate-precipitated fraction from mycelia and culture-filtrates and the crude, cell-free culture filtrates from the growth medium of the fungi Chrysosporium palmorum, Eurotium rubrum, Micromucor isabellina, and Pythium aphanidermatum when aseptically added to cell suspensions of Cantharanthus roseus caused a rapid and dramatic increase in indole alkaloid biosynthesis. Up to 400 micrograms/L ajmalicine and 600 micrograms/L catharanthine were detected in C. roseus cell suspension grown in the presence of the M. isabellina fungal culture filtrate for 3 d. Untreated cells produced only trace levels of ajmalicine and catharanthine per liter of cell suspension after 15 d of culture.
Cell Line↗
Effects of quinidine and cimetidine on methamphetamine stereotypy in rats.
The effects of quinidine and cimetidine on methamphetamine-induced stereotyped behavior were studied in rats. Quinidine (10, 30 and 50 mg/kg) and cimetidine (100, 250 and 500 mg/kg) were administered orally 60 min prior to subcutaneous injection of a fixed dose of methamphetamine (5 mg/kg). It was found that quinidine and cimetidine very markedly potentiated the intensity of methamphetamine stereotypy. The duration of the stereotypy in the group pretreated with either drug was 2.3-4.0 times longer than that in the control group. Furthermore, the urinary pH levels of rats were measured after administrations of methamphetamine alone and of methamphetamine following the drugs in question. Urinary pH was not changed by pretreatments with those drugs, suggesting that the enhancing effects of quinidine and cimetidine on methamphetamine-induced stereotyped behavior are not derived from a change in urinary pH level. The enhancement of methamphetamine-induced stereotyped behavior may be explained by inhibitory effects of quinidine and cimetidine on the metabolism of methamphetamine.
Animals↗
Effects of quinidine and cimetidine on the methamphetamine level in the rat brain.
The drug interaction between methamphetamine and quinidine/cimetidine was investigated in terms of distribution of methamphetamine to the brain. The concentrations of methamphetamine and amphetamine in the brain after an s.c. injection of methamphetamine were determined in rats pretreated with a single oral dose of quinidine or cimetidine. Both drugs markedly enhanced the increase in the concentrations of methamphetamine and its metabolite, amphetamine. These results suggest that the recent finding of the enhancements of the behavioral effect of methamphetamine by quinidine and cimetidine is due to the increase in levels of methamphetamine and amphetamine in the brain by these pretreatment drugs.
Amphetamine↗
The effect of trans-4-guanidinomethylcyclohexanecarboxylic acid p-tert-butylphenyl ester hydrochloride (NCO-650) on Ascaris suum antigen-induced bronchoconstriction in dogs.
Antiallergic asthma effect of trans-4-guanidinomethylcyclohexane-carboxylic acid p-tert-butylphenyl ester hydrochloride (NCO-650), a new anti-allergic drug, was investigated in comparison with those of tranilast and disodium cromoglycate (DSCG) in anesthetized dogs. The asthmatic bronchoconstriction was induced by inhalation of Ascaris suum antigen (Asc-Ag) to naturally Ascaris-sensitive dogs. The airway resistance was determined using the modified Konzett-Rössler method. Both intravenous (1 and 5 mg/kg) and intraduodenal (10, 30 and 100 mg/kg) administrations of NCO-650 prior to the antigen challenge markedly inhibited the asthmatic bronchoconstriction induced by Asc-Ag inhalation. The antiasthmatic effect of NCO-650 was much stronger than that of DSCG (10 mg/kg, i.v.) and was about three-fold stronger than that of tranilast. On the other hand, when NCO-650 was administered after the antigen challenge, the agent had no inhibitory effect on the Asc-Ag induced bronchoconstriction. As for the effects on increased airway secretion at the time of asthmatic attack, NCO-650 inhibited the excessive secretions without any remarkable change in the viscosity of the secretions. NCO-650 had no effect on the bronchoconstriction induced by inhalation of acetylcholine, suggesting that NCO-650 appears to have no anti-cholinergic effect and thus no effect on the vagal reflex that occurred during the asthmatic responses. The above findings show that NCO-650 may be useful for the treatment of bronchial asthma as an orally active drug.
Acetylcholine↗
The effects of chlorpheniramine and antiallergic drugs on Ascaris suum antigen-induced active cutaneous anaphylaxis in dogs.
Effects of chlorpheniramine and two antiallergic drugs on the active cutaneous anaphylaxis (ACA) reaction induced by intradermal injection of Ascaris suum antigen in naturally sensitized dogs were investigated. Chlorpheniramine (10 mg/kg, intraduodenally (i.d.)) almost abolished the ACA reaction. NCO-650 (100 mg/kg, i.d.) had no inhibitory effect, while tranilast (300 mg/kg, i.d.) showed a weak inhibitory effect. These findings show that the ACA reaction is almost totally mediated by histamine and ACA reaction is considerably resistant to antiallergic drugs such as tranilast and NCO-650.
Anaphylaxis↗