摘要:

Abstract:The influence of histamine on the level of cyclic AMP was studied in human platelets. A dose‐related accumulation of cyclic AMP was obtained, culminating at about 10 μM of histamine. The response was blocked by the H2antagonist cimetidine, but neither by H1antagonists nor by α‐ or β‐adrenergic antagonists. The results suggest that histamine causes an accumulation of cyclic AMP in human platelets by stimulation of H2receptors. Cyclic AMP accumulation is supposed to be associated with a depression of the platelet function, and a reduced platelet release reaction was actually demonstrated by our

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb01650.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Abstract:Intravenous injection of isoprenaline and salbutamol into rats caused an inhibition of the spontaneous contractions of uterus and increased the uterine cAMP level in a dose‐dependent manner. The effects of isoprenaline (0.036 nmol/kg) were diminished or completely prevented by propranolol (0.07–7 μmol/kg). Intravenous infusion of the β‐adrenergic agonists during one hour increased the uterine cAMP level. The highest level of cAMP measured was at 3 min. after start of infusion, thereafter it declined first rather fast but later more slowly. This time pattern of cAMP was very similar to what was seen during incubation of uterine tissue with isoprenalinein vitro. Pretreatment with isoprenaline three times daily 4–7 days before the experiments, decreased both the degree of inhibition and the increase of cAMP in uterus caused by an intravenous injection of isoprenaline. A slight effect on the cAMP rise was detectable after one day of pretreatment, and it seemed to have reached its maximal effect after 4 days, since no further decline in the cAMP response was seen when the pretreatment was prolonged. A desensibilization to P‐adrenergic agonists was thus seen in uterus after excessive stimulation of isoprena

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb01651.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Abstract:Thymoxamine, 6‐acetoxythymol‐2‐dimethylaminoethyl ether, is a competitive α‐adrenoceptor blocking agent used as a vasodilator in the treatment of peripheral vascular disorders. The plasma half‐life of the drugin vivois very short.In vitroexperiments showed that thymoxamine had a half‐life in human plasma of about only 1 min. By using the compound as a substrate in increasing concentrations from 5–320 μg/ml in the presence of a fixed, low concentration of plasma (0.1 % v/v) at pH 7.4 and 37° a hyperbolic correlation was found between the concentration of thymoxamine and the intial rate of formation of the involved reaction product, which was determined by HPLC. A linearized Michaelis‐Menten plot indicated an enzymatic biotransformation. A Km‐value of about 0.115 μmol ml−1and a Vm‐value of about 0.0037 μmol ml−1min.−1were found. Physostigmine, neostigmine and cinchocaine inhibited the biotransformation competitively. This indicated that plasma cholinesterase was the enzyme responsible. The metabolite was identified as desacetylthymoxamine by HPLC, spectrophotometry and

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02018.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Abstract:Acute intravenous toxicity and pharmacological properties of surface‐active alkyltrimethylammonium bromides (C10‐C20) were studied in female rats. The acute toxicity of the surfactants decreased with an increasing length of the alkyl chain up to a chain length of 16 carbon atoms. Death appeared to be due to respiratory failure. The twitch responses of sciatic nerve‐gastrocnemius muscle preparations were reversibly depressed at direct and indirect stimulation following intravenous injections of sublethal doses of C10‐C14. Doses blocking the twitch responses of indirectly stimulated gastrocnemius corresponded to about half the LD50, and at these doses C10‐C14caused a transient decrease in respiratory rate. The C16homologue caused respiratory arrest without affecting the twitch responses of gastrocnemius at relative low intravenous doses. Sublethal intravenous doses of C12‐C20caused, apparently due to vasodilatation, a tarnsient fall in arterial blood pressure. The depressor response increased and the twitch response decreased with an increase in the length of the alkyl chain up to a chain length of 16 carbon atoms. Both the depression of skeletal muscle contraction and the vasodilatation is suggested to originate from a non‐specific effect of the surfactants on

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02019.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Abstract:An ultra filtration method is described by which it is possible to estimate the protein bound fraction of a drug at its original concentration in a serum sample. The determination is carried out at 37° and pH 7.4. For thiopental no difference was found between the values of protein binding whether they were determined by the ultrafiltration method or by a less time consuming equilibrium dialysis against an equal volume of phosphate buffered isotonic sodium chloride solution. The equilibrium dialysis was used to measure the concentration of bound and unbound thiopental molecules; and the binding parameters in a two class binding model were determined. No evidence was found for binding to other proteins than albumin. About one binding site belonging to the first class was found per 1000 albumin molecules whereas an average of about 5 secondary sites were found for each albumin molecule. The association constants for the primary class of binding sites were 3.4×106M−1for albumin and 13.3×106M−1for serum while the values for the secondary class were 2.2 and 1.2×103M−1for albumin and serum respectively. The estimates of association constants and number of binding sites were based on experiments with total thiopental concentrations ranging from 0.4 to 80 μg/ml. In a phosphate buffered albumin solution with 2 g albumin per 100 ml, a pH increase from 5 to 8 caused an increase in protein binding from 36 to 76%. A Scatchard plot using data from experiments with increasing albumin concentrations resulted in a “plot” with positive slope. The use of a curve like this is discussed and it is concluded that the binding parameters for thiopental are influenced by the albumin

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02020.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Abstract:The disappearance and reappearance of iron‐59 in plasma and blood at various time intervals has been studied in control, manganese, nickel and tin administered and anaemic rats after a single intravenous injection of an aqueous solution of radioactive iron (III) citrate. Significant difference was observed in the rate of reappearance of iron‐59 in the circulation between control and manganese treated animals. The disappearance of iron‐59 from the plasma of control and treated animals however did not show any appreciable difference. A significant increase in the radio‐iron content was observed in bone marrow, liver and kidney of treated animals as compared to control group forty eight hours afte

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02021.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Abstract:The uptake of14C‐chloroquine by isolated mouse pancreatic isletsin vitrowas investigated. The islets were found to have a very high capacity to accumulate the substance. The uptake of14C‐chloroquine in the islets was a saturable process. Metabolic inhibitors, oubain, anaerobic conditions and absence of glucose did not inhibit the uptake of14C‐chloroquine in the slets, suggesting that the substance is accumulated by some means other than energy‐dependent active transport or pinocytosis. The uptake ofl4C‐chloroquine was inhibited by low temperature and low pH and in the presence of mepacrine, chlorpromazine, imipramine and desmethylimipramine. Only a small part of the14C‐chloroquine which had been taken up in the islets left the cells during 45 min. incubation in non‐radioactive media. Two possible mechanisms for the uptake of14C‐chloroquine in the islets are considered: (1) The accumulation may be due to a binding of the substance to cellular constituents. (2) Chloroquine may be trapped by protonation within lysosomes or other membrane‐surrounded organ

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02022.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Abstract:This study was aimed at the question of whether or not the antidepressant zimelidine, which is an amphiphilic cationic compound, can induce generalized lipidosis in animals. Rats were chronically treated with high oral doses (80 mg/kg) of the drug, and several organs were examined by light and electron microscopy. Lipidosis‐like cellular alterations of considerable degrees were observed in lung, adrenal cortex and lymphatic tissue. Only mild lysosomal alterations were found in hepatocytes, adrenal medulla, retinal pigment epithelium and in peripheral and central nerve cell perikarya. The results show that zimelidine induces generalized lipidosis in rats although of mild degree when compared with some other amphiphilic cationic drug

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02023.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Abstract:We have incubated the local anaesthetic drug lidocaine with microsomes from human adult livers. The metabolites deethylated lidocaine (MEGX) and aromatically hydroxylated lidocaine (3‐hydroxylidocaine) were isolated by high performance liquid chromatography and quantitated by the liquid scintillation counting technique. The deethylation rate markedly exceeded the hydroxylation rate also at very low lidocaine concentrations. This pattern differs from that detected earlier with rat liver microsomes where aromatic hydroxylation is significant at low lidocaine concentrations, but it is similar to that in female guinea pig microsomes. These findings show the importance of performing this type of experiments also with human material

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02024.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY

摘要:

Abstract:Amitriptyline, nortriptyline and their metabolites, desmethylnortriptyline, cis and trans 10‐hydroxyamitriptyline, cis and trans 10‐hydroxynortriptyline and amitriptyline‐N‐oxide, have been tested for inhibitory effect on the uptake of serotonin (rabbit thrombocytesin vitro) and noradrenaline (mouse atriain vitroand mouse heartin vivo), for anticholinergic activity (guinea‐pig ileumin vitro) and for antagonism against tetrabenazine induced inactivity as well as apomorphine and 5‐hydroxytryptophan potentiating effect in mice. Amitriptyline inhibits serotonin and noradrenaline uptake equally, whereas nortriptyline is a more potent inhibitor of noradrenaline than of serotonin uptake. The metabolites resemble nortriptyline in this respect. The 10‐hydroxylated metabolites are equipotent with amitriptyline as regards noradrenaline uptake inhibition. All the metabolites are less anticholinergic than amitriptyline and nortriptyline. Thein vitroresults are reflected in thein vivobehavioural tests, although some discrepancies are found, probably due to differences in absorption, distribution, metabolism and excretion. The importance of knowledge concerning pharmacological properties of the metabolites in comparison with amitriptyline and nortriptyline for correlating plasma levels of these and their metabolites to clinical outcome

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1980.tb02025.x

出版商:Blackwell Publishing Ltd    

年代:1980

数据来源: WILEY