摘要:

AbstractThe purpose of the present study was to define the elimination kinetics of phenazone (NFN) in the isolated perfused pig liver. In five experiments phenazone was administered as constant infusion to obtain steady‐state periods over a wide range of concentrations. The elimination of phenazone followed saturation kinetics (concentrations 0.1–12 μmol × 1‐1) and the maximal elimination rate (Vmax) was on average 102 μmol × min.‐1× kg‐1liver and the Michaëlis‐constant (Km) of 2.6 mmol × 1‐1. Estimates of Vmaxand Kmfor the microsomal phenazone hydroxylase activity measured in liver biopsies were found to be considerably lower than in the perfused liver. The hepatic elimination of phenazone during perfusion of pig liver at phenazone concentrations corresponding to human therapeutic doses follows

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02048.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe corpus‐fundus of the urinary bladder of man and cat was studiedin vitrowith respect to type of beta‐adrenergic receptors. In both species beta‐adrenergic stimulation produced marked relaxation but species differences were apparent. In the cat bladder only beta1receptors were found. In the human bladder the beta‐receptors had neither beta1‐ nor beta2‐characteristics. It is suggested that the beta‐adrenergic receptors in the corpus‐fundus of the human bladder are

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02049.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractTo study how acetylation affects the activity of sympathomimetic amines the effects of tyramine, amphetamine ephedrine, phenylephrine, orci‐prenaline and salbutamol and of their O‐ and N‐acetyl derivatives on blood glucose and free fatty acid concentrations were studied in the rabbit. Hyperglycemia was induced by all parent compounds except amphetamine which tended to have a weak hypoglycaemic action. Hyperlipaemia in the doses used was induced by ephedrine and orciprenaline but not by the other parent compounds. Usually acetylation decreased the metabolic effects of the compounds but O‐acetylation of tyramine and salbutamol caused hyperlipaemia and O‐acetylation of ephedrine increased its fatty acid‐mobilizing action, perhaps as a consequence of increased lipid solubility of the compounds. The ultimate effects of the O‐acetyl derivatives were probably at least partly due to deacetylation at their sites of action. Hence O‐acetylation of sympathomimetics could perhaps be used to induce dr

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02050.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe effects of acetylation of sympathomimetic amines, tyramine, amphetamine, ephedrine, phenylephrine, orciprenaline, and salbutamol, and their O‐ and N‐acetyl derivatives and the effects of reserpine or physostigmine pretreatment on the isolated auricles and tracheal chain of guinea‐pigs have been studied. All the parent drugs relaxed the tracheal chain and had a positive inotropic and chronotropic effect on the isolated auricles; only amphetamine, on the contrary, contracted the tracheal chain. O‐acetylation of these sympathomimetic amines generally decreased less chronotropic than inotropic action on the isolated auricles. O‐acetylation of tyramine however: actually increased the positive chronotropic activity of drug. As a rule, O‐acetylation also decreased the beta‐adrenergic effect of these compounds on the tracheal chain, but not so markedly as on the isolated auricles. N‐acetylation generally abolished the adrenergic effects of these sympathomimetic amines on the isolated auricles and decreased those effects on the tracheal preparation. N,O‐triacetylation of salbutamol abolished the stimulating effect of the parent drug on the auricles but increased the relaxant activity on the trachea. Physostigmine antagonized the effects of O‐acetyltyramine and O‐triacetylorciprenaline but not those of tyramine and orciprenaline on the trachea preparation. It is concluded that among the sympathomimetic amines acetylation may be utilized for the development of specific bronchodilators and O‐acetylation for ind

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02051.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe bronchodilator effect of QH25 (3‐(4‐methoxybenzylamino)‐4‐hydroxy‐α‐(tert. butylaminomethyl)benzylalcohol, HCl) a new beta2‐adrenergic bronchodilator has been investigated in conscious guinea pigs and in anaesthetized guinea pigs and cats and compared to that of salbutamol and isoprenaline. In anaesthetized guinea pigs QH25 and isoprenaline were equipotent after intravenous administration, whereas salbutamol was four times less active. The same difference between QH25 and salbutamol was observed after intraduodenal administration. After oral administration in conscious guinea pigs QH25 was eight and five times more potent than salbutamol and isoprenaline respectively, whereas no difference was observed when the agents were administered as aerosols. The bronchodilator action of QH25 was approximately three times that of salbutamol in egg‐albumine sensitized guinea pigs after oral administration. In anaesthetized cats the bronchodilator potency of QH25 was three times that of salbutamol and the same or slightly higher than that of isoprenaline. A half‐life of 4 hours for the bronchodilator action in guinea pigs was determined for both QH25 and salbutamol after oral administration. The effect of QH25 and salbutamol on cardiovascular parameters i. e. chrono‐ and inotropic action and blood pressure decreasing effect in guinea pigs, cats and dogs was essentially the same whereas isoprenaline was from 5 to 30 times more potent. The potential tremorogenic action of QH25 estimated on the cat soleus muscle was eight times less than that of isoprenaline and the same or slightly less than that of salbutamol. From the experimental data it is concluded that QH25 has the same potency as isoprenaline as a bronchodilator agent but is more potent than salbutamol. Taking into account that isoprenaline is considerably more active on cardiovascular parameters and on the cat soleus muscle than QH25 which has the same or less effect than salbutamol on these parameters the data suggest that QH25 is a more selective bronchodilator agent than both isopren

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02052.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractA method for the separation of urine and faeces in the hen was developed and the biological fate of32P malathion, following a single oral dose of 262.40 mg/kg body weight was studied. The results suggested that the compound was rapidly absorbed from the gastrointestinal tract; significant quantities being detected in the plasma and whole blood1/2hr after ingestion. Total32P was eliminated in the urine by apparent first order kinetics with an average half‐life of 5.7 hrs. The cumulative urinary and faecal data revealed that 93 % of the32P is excreted via the urine within 48 hrs, thus indicating that the compound is almost completely absorbed. It is therefore concluded that accumulation in the system is unlikel

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02053.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractA decreased glutathione peroxidase (GPX) activity was demonstrated in erythrocytes from 12 patients with neuronal ceroid lipofuscinosis (NCL). The enzyme activity was corrected to normal levels by selenium (Se) supplementation.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02054.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe influence of surgical anaesthesia induced by ketamine, pentobarbital, pentobarbital‐xylazine, or chloralose‐urethane on blood pressure and heart rate was studied, and the effects were compared with results in conscious and pithed rats. The blood pressure was significantly decreased by pentobarbital‐xylazine. The heart rate increased in all groups except in pentobarbital‐xylazine anaesthetized rats. Generally, a fall in heart rate and blood pressure was observed during a two hours lasting anaesthesia as compared to the initial values. The blood pressure response to noradrenaline was significantly lowered by ketamine, pentobarbital and chloralose‐urethane anaesthesia, and the response of the heart rate only by chloralose‐urethane. Guanethidine 5 mg/kg intravenously significantly lowered the blood pressure in the ketamine, pentobarbital and chloralose‐urethane anaesthetized groups. The guanethidine induced potentiation of the haemodynamic effects of noradrenaline was considerably influenced by the anaesthetic, the augmentation being greatest in pentobarbital and chloralose‐urethane anaesthetized rats. Chloralose‐urethane is considered a suitable anaesthetic in rats when studying the effects of noradrenaline and guanethidine. Following a single intraperitoneal injection a surgical anaesthesia of more than two hours' duration was obtained, and the variance of the parameters studied was less than that following administration of the other anaesthetics. It is emphasized that various effects of anaesthetics unrelated to their anaesthetic properties may obscure or even invalidate results obtained with drugs acting on the peripheral sympathet

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02055.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe efflux of3H‐bretylium in rat vas deferensin vitroevoked by a number of sympathomimetic amines was examined. The tissue was preloaded with3H‐bretylium (2 × 1‐7M) and the efflux of bretylium to the incubation medium in the presence of the amines during 20 rnin. was determined. The efflux evoked by (+)‐amphetamine was almost abolished at 0° and by desipramine. The dose response curves showed that some of the amines at high concentrations markedly antagonized their own effect. It could be demonstrated that (+)‐amphetamine and N‐methylamphetamine at a high concentration also antagonized the efflux evoked by low external Na+concentration and it is suggested that this effect is produced by inhibition of the outward transport of bretylium through the neurone membrane. The structure activity relationship obtained shows that the non‐hydroxylated amines are most potent in evoking bretylium efflux and that the potency diminished with the number of hydroxyl groups. The tertiary amine analogue of amphetamine is less active and the quaternary derivative much less active than amphetamine and N‐methylamphetamine. A hydroxyl group at 3‐position gives a somewhat higher potency than that at 4‐position. This structure activity relationship is similar to that previously reported for the sympathomimetic amines in reversing the adrenergic neurone blockade by bretylium and it is proposed that this reversal is induced by the reduction of the intraneuronal concentration of bretylium as a result

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02056.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe kinetics of nortriptyline in four patients were investigated before and during treatment with perphenazine (24–36 mg/day) by administering 57 mg nortriptyline hydrochloride as an intravenous infusion and evaluating the resulting plasma concentration data according to a two compartment open model. In all patients an increased biological half‐life as well as a decreased systemic clearance and rate of metabolism were found in the perphenazine‐period, thus confirming the inhibitory effect of perphenazine on the metabolism of nortriptyline found in earlier studies. Some interaction with distribution parameters was also indicated, but on the whole the model parameters did not provide much further information about the interaction. Although the most pronounced changes were found with the patient getting the highest dose of perphenazine, the dose‐effect relationship remains

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02057.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY