摘要:

AbstractThe effects of two pure chlorobiphenyls (2,4′,5–trichlorobiphenyl and 2,2′,4,4′,5,5′–hexachlorobiphenyI) on the hepatic drug metabolizing system, and the elimination rate from the liver of the two chlorobiphenyls have been studied in the female mouse. The results obtained show that: 1. The two chlorobiphenyls are both potent inducers of the hepatic drug metabolizing system. 2. The hexachlorobiphenyl is a more potent inducer of the hepatic drug metabolizing system than the trichlorobiphenyl. 3. The trichlorobiphenyl is eliminated from the liver much faster than the hexachl

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03165.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe inhibition of the uptake of3H–(–)–noradrenaline (NA),3H–dopamine and14C–5–hydroxytryptamine (5–HT) in mouse brain slices by (Z)–3–dimethylamino–l–(4–bromophenyl)–l–(3–pyridyl)propene (H 102/09), desipramine and chlorimipramine and their releasing effect on the3H–amines previously accumulated in the slices were examined. The interactions with reserpine produced hypothermia and sedation and the 5–hydroxytryptophan (5–HTP) syndrome in mice were also studied. Due to the poor inhibitory activity on the NA uptake H 102/09 was a more selective inhibitor of the 5–HT uptake than was chlorimipramine, particularly after administrationin vivo,where it was as potent as chlorimipramine (ED50 = 19 μmol/kg intraperitoneally).In vitrochlorimipramine was 6 to 12 times more active than H 102/09. Desipramine was a very selective inhibitor of the NA uptakein vitroandin vivo.The compounds were generally more potent in inhibiting the uptake than in releasing the amines. However, in striatal slices the inhibition of DA uptake could be due to the releasing effect since the difference in potencies were small. The effect of desipramine on 5–HT uptake and that of H 102/09 on NA uptake could also involve a release component. The 5–HTP syndrome was potentiated by H 102/09 and chlorimipramine but not by desipramine. The reserpine hypothermia but not the sedation was potently antagonized and reversed by desipramine and by chlorimipramine at high doses but not by H 102/09, suggesting that NA but not 5–HT is inv

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03166.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe intravesical pressure and volume of the urinary bladder of anaesthetized rabbits were studied using a urinary bladder infusion technique. It was shown that the anticholinergic compounds used, atropine, emeprone, and PR 197, significantly increased the urinary bladder volume capacity, and that they decreased the micturition pressure. Atropine was the most potent compound in increasing the bladder volume capacity, followed by PR 197 and emeprone, mentioned in order of potency. Atropine and PR 197 increased the bladder volume capacity and the micturition threshold pressure significantly more than emeprone. There was no statistically significant difference between the effects of the different compounds on the residual volume or the micturition pressure. It is suggested that the effects of the compounds are confined mainly to the bladder and most probably to its cholinergic structures.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03167.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThree anticholinergic compounds, atropine, emeprone, and PR 197 (synthesized at AB Recip, Sweden), were tested for their effects on the infused urinary bladder of unanaesthetized rabbits. Following the injection of emeprone and PR 197 (1–4 mg/kg intravenously) the bladder volume capacity increased and the micturition pressure decreased. These drugs also produced a residual volume after micturition. No change in the micturition threshold pressure could be detected. Atropine (1–4 mg/kg intravenously) caused a marked decrease in the bladder volume capacity, micturition pressure, and micturition threshold pressure, but did not produce any residual volume. The results obtained in the present investigation using unanaesthetized animals differed from similar experiments, where anaesthetized animals were used. It is concluded that the peripheral actions of the substances used were confined mainly to the cholinergic receptors in the urinary bladder. The different response after atropine was attributed to its central stimulating eff

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03168.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractRats of the Wistar/Af/Han/Mol/(Han 67) strain were preselected for the inducibility of the hepatic soluble aldehyde dehydrogenase, after treatment with phenobarbital (80 mg/kg daily, intraperitoneally, for 4 days) and open liver biopsy. Animals with highly induced aldehyde dehydrogenase also had a 50 and 40 % difference in the induction of D–glucuronolactone dehydrogenase and NADPH–cytochromecreductase respectively. Other enzymes of the hepatic drug hydrox–ylation and glucuronidation did not show significant variation in the induction pattern between the two genetic groups. After inbreeding, the second filial generation was used in order to determine enzyme activities without any pretreatment. The basal activities of aldehyde and D–glucuronolactone dehydrogenase, but not of NADPH–cytochromecreductase, were also different in the untreated animals. Urinary excretion of D–glucaric acid was the same in the two groups, both in the basal and the in

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03169.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractStrips from human pregnant and non–pregnant uteri were examinedin vitro.The spontaneous contractions were more frequent in the strips from nonpregnant uteri. Isoprenaline inhibited the contractions of the strips from pregnant uteri, while the strips from non–pregnant uteri were much less sensitive to isoprenaline. Propranolol antagonised the effect of isoprenaline on strips from pregnant uteri, the dissociation constant for propranolol being of the magnitude 10–8. Carbacholine contracted the strips from non–pregnant uteri. The effects of isoprenaline on spontaneously contracting and carbacholine–contracted strips were compared quantitatively, and were found to be of the s

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03170.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe effects of isoprenaline, isoxsuprine and ritodrine were tested on spontaneously contracting muscle strips from non–pregnant human uterusin vitro.The strips were rather insensitive to all three drugs, the maximal inhibitions obtained being: isoxsuprine (10–4M) 81 %, ritodrine (10–4M) 45 %, isoprenaline (10–5M) 19%. Propranolol 3.4 × 10–6M did not significantly block the effects of isoxsuprine and ritodrine. It is concluded that the non–pregnant human uterus is rather insentitive to β–adrenoceptor stimulation, and that isoxsuprine and ritodrine act mainly through unspec

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03171.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe acute subcutaneous toxicity of isoprenaline was found to depend on body temperature. Since isoprenaline increases both heat production and heat loss, its effect on body temperature was influenced by the thermoregulatory capacity of an animal. An increased hyperthermic action of the drug following a rise in ambient temperature by 4° was associated with 10 times increased toxicity. Increased heat production capacity following cold acclimatisation resulted in increased toxicity at room temperature but no more than in a cold environment. The higher body weight to body surface ratio in bigger rats diminished the isoprenaline–induced hypothermia. On the other hand, hypothermia reduced tachycardia and pulse pressure responses to isoprenaline. However, cardiomegaly and myocardial lesions produced by small and repeated doses of isoprenaline (5 mg/kg daily for 4 days) were independent of whether the animals were hypo– or hyperthermic after the injections. In addition, the extent of cardiac enlargement was as great in small rats as in the larger rats. It is concluded that hypothermia protects the heart from acute failure but not from hypoxia, which may be the main reason for cardiomegaly and myocardial lesions after isoprena

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03172.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe bronchospasmolytic and cardiovascular effects of terbutaline and ibuterol were tested in the anaesthetized cat after inhalation and after intravenous infusion. A 5–min. inhalation of ibuterol in the concentrations 0.01–0.5 mM counteracted the serotonin–induced bronchoconstriction. In this respect it was 3 times as potent as terbutaline. The two compounds administered intravenously proved equi–effective. Neither inhalation nor intravenous infusion had any significant effect on the heart rate, pulse amplitude, or arterial blood pressure, in doses which counteracted the induced bronchospasm. Higher doses of the compounds caused a dose–dependent increase in heart rate and pulse amplitude, and a decrease in diastolic blood pressure. After intravenous infusion, the cardiovascular effects of the compounds were almost identical. Inhaled ibuterol had a more pronounced effect than inhaled terbutaline. It was concluded that both ibuterol and terbutaline, have a good margin between the bronchospasmolytic and the cardiovascular effects after inhalation and intravenous infusion. Esterification of the OH–groups in the ring of terbutaline with di–isobutyric acid did not change

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03173.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractPrevious experiments suggested that the positive inotropic response to α–adrenergic stimulation was unrelated to cyclic AMP in contrast to the inotropic effect of β–adrenergic stimulation. In order to elucidate this question further we perfused hearts from rats made hypothyroid by treatment with propyl–thiouracil, since this treatment is known to augment the myocardial α–adrenergic effects. α–stimulation (phenylephrine in the presence of propranolol) caused a marked inotropic response and no increase in cyclic AMP. In contrast β–stimulation (isoprenaline) increased the cyclicAMPcontent. The time–courses of the inotropic responses to α– and β–stimulation were different. The aortic pressure waves indicated a shorter duration of each contraction phase after isoprenaline than after phenylephrine in the presence of propranolol. This difference is probably due to the cyclic AMP accumulated after isoprenaline. The findings support the hypothesis that the positive inotropic effect of α–adrenergic stimulation is caused by mechanisms independent of cyclic AMP, while the β–adrenergic inotropic effect involves cyclic AMP mediated processes. Such a dual mechanism of action for adrenergic agents might serve to maintain responsiveness of the

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03174.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY