摘要:

Evidence for and against heterogeneity in the histamine H2-receptor population is reported: it was based on different degrees of potency and also of efficacy among the H2-receptor-selective agonists; less striking but still evident differences in the potency of H2-antagonists; atypical interactions between H2-agonists and antagonists in particular experimental conditions and finally inability of H1- and H2-receptor antagonists to block some of the effects of histamine. Binding studies gave equivocal results. All the data reported in this review suggest that, although it is premature to speak about H2-receptor subtypes, further investigations are needed to check whether or not H2- and perhaps also H1-receptors represent homogeneous populations of histamine receptors.

ISSN:0031-7012    

DOI:10.1159/000137522

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

Acid extracts of porcine pancreas acetone powders (but not of other tissues) have been shown to contain material which will react firstly in a radioimmunoassay for beta-endorphin, and secondly, compete with 3H-Naloxone and 3H-enkephalinamide in the radio-receptor assay. This material had a molecular weight of approximately 7,000 as judged by both P-10 and G-50 exclusion chromatography, even in the presence of 4 M urea. The G-50 partially purified and desalted fraction demonstrated a dose-dependent analgesia in mice and also influenced mouse behavior in vivo in a manner analogous to that produced by synthetic human beta-endorphin.

ISSN:0031-7012    

DOI:10.1159/000137523

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

27 male volunteers aged 20 to 91 years, and 13 female volunteers aged 21 to 33 years, received single 5 to 10 mg doses of diazepam intravenously. Diazepam pharmacokinetics were determined from concentrations measured in multiple plasma samples drawn during 7 days after each dose. Diazepam elimination half-life among males (mean: 66 h) increased significantly with age (r = 0.53, p < 0.005). Volume of distribution (mean: 1.39 liters/kg) also increased significantly with age (r = 0.67, p < 0.001). Clearance of total diazepam in males (mean: 0.42 ml/min/kg) tended to decline with age (r = 0.32), but the association was of borderline significance (p = 0.1). Diazepam was extensively bound to plasma protein, with a mean free fraction among male subjects of 1.34%. Free fraction tended to increase with age (r = 0.14). Correction of volume of distribution and clearance for individual differences in binding did not alter the conclusions. Compared to young males, young females had larger volumes of distribution (1.87 vs. 1.34 liters/kg) and higher total clearance (0.63 vs. 0.49 ml/min/kg). These differences were even greater after correction for sex-related changes in protein binding. Elimination half-life did not differ between sexes. Since both age and sex can influence diazepam disposition, both should be considered as independent variables in studies of diazepam pharmacokinetics.

ISSN:0031-7012    

DOI:10.1159/000137524

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

Several possible mechanisms capable of inducing the anti-bronchoconstrictor effects of eprozinol have been investigated in vitro by means of the following techniques: (l)test for inhibition of mast cell histamine release, secondary to a passive anaphylactic response on human lung tissue; (2) determination of the type of interference with the contracting effects of bradykinin, acetylcholine and serotonin; (3) interference with the smooth muscle contraction induced by BaCl2 or CaCl2; (4) investigation of blockade by propranolol of eprozinol-induced relaxation of tracheal muscle; (5) investigation of changes in cAMP and cGMP levels in guinea pig trachea; (6) investigation of an inhibitory effect on phosphodiesterase. When the immunological reaction is carried out while eprozinol is in contact with the lung preparation, the compound appears more effective than disodium cromoglycate but less effective than isoprenaline in inhibiting mast cell degranulation. In fact, a 40% inhibition of mast cell histamine release occurs with a concentration of eprozinol at 2 x 10–6M. On the other hand, when the preparations are rinsed between the period of incubation with the compound and the addition of antigen, only disodium cromoglycate still manifests significant inhibitory activity. Eprozinol antagonises serotonin, bradykinin and acetylcholine in a non-competitive fashion (pD2 = 4.21 ± 0.09; 3.81 ± 0.07 and 4.17 ± 0.07, respectively). Eprozinol non-specifically antagonises BaCl2 (ileum or tracheal muscle from the guinea pig) and CaCl2 (KC1-depolarised guinea pig caecum). The relaxant effects on calf tracheal smooth muscle are characterised by the following parameters: isoprenaline, pD2 = 7.93 ± 0.21 and eprozinol, pD2 = 4.37 ± 0.17. With guinea pig trachea, these parameters are: isoprenaline, pD2 = 6.7 ± 0.10 and eprozinol, pD2 = 2.5 ± 0.09. In all cases the intrinsic activity of both compounds is the same (α = 1). No significant changes in cAMP and cGMP levels are observed in guinea pig trachea, with eprozinol or isoprenaline, at doses capable of inducing relaxation. Eprozinol is only a very weak phosphodiesterase inhibitor, at large conce

ISSN:0031-7012    

DOI:10.1159/000137525

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

The possible interactions of the anti-asthmatic compound, eprozinol, with bronchoconstrictors and adrenergic agents were investigated in the anaesthetised guinea pig by means of the following techniques: (1) study of the inhibition of histamine- and serotonin-induced bronchospasm; (2) investigation of potentiation or antagonism beween the anti-bronchoconstrictor effects of eprozinol and isoprenaline; (3) investigation of propranolol-induced blockade of the anti-bronchoconstrictor effects of eprozinol and several reference compounds. In the anaesthetised guinea pig, eprozinol (5 mg kg–1), isoprenaline (2 µg kg–1) and theophylline (15 mg kg–1) administered intravenously cause a clear inhibition of the bronchospasm induced by intravenous perfusion of histamine or serotonin, with an intensity not significantly different for all three compounds. The anti-bronchoconstrictor activities of eprozinol and isoprenaline with regard to histamine are directly additive and show absolutely no interference with one another. Propranolol is without effect on in vivo anti-bronchoconstrictor activity of eprozinol on tracheal musculature. It is concluded that the mechanisms brought into play by eprozinol to exert anti-bronchoconstrictor and bronchorelaxant activity, are completely independent of the adrenergic

ISSN:0031-7012    

DOI:10.1159/000137526

出版商:S. Karger AG    

年代:1981

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000137527

出版商:S. Karger AG    

年代:1981

数据来源: Karger