Inhibition by furosemide of inflammatory mediators from lung fragments.
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Depression, Chemical↗
Biomedical subjects
D M Temple
Publications and source records attributed to D M Temple.
Metabolism and disposition of indomethacin in preterm infants.
38 preterm infants with symptomatic patent ductus arteriosus received indomethacin intravenously. Plasma samples were collected at 2, 4, 6 or 8 and 12 h after each of 3 doses. Indomethacin, demethylindomethacin and p-chlorobenzoic acid were determined in plasma and urine along with acid-labile metabolites using HPLC. Fifty-eight percent of the infants demethylated indomethacin; half of the unchanged and demethylated drug was found as conjugates in urine; 14% deacylated the drug. Shorter elimination half-life, smaller area under the plasma concentration-time curves and increased plasma clearance were associated with demethylation. Postnatal age greater than 2 weeks correlated with both demethylation and failure of indomethacin to effect ductal closure.
Birth Weight↗
Nedocromil sodium inhibits antigen-induced contraction of human lung parenchymal and bronchial strips, and the release of sulphidopeptide-leukotriene and histamine from human lung fragments.
1. The effects of nedocromil sodium on antigen-induced release of sulphidopeptide-leukotrienes and histamine from passively sensitized fragments of human lung, and on antigen-induced contraction of sensitized strips of human lung parenchyma and bronchus, have been studied. 2. Nedocromil sodium 0.1 and 1 microM inhibited leukotriene release from fragments of human lung by 30% and 38% respectively, and histamine release by 43% for both concentrations, but 10 microM was ineffective. The lung fragments, which were passively sensitized to house dust mite, Dermataphagoides pteronyssinus, in control experiments released leukotrienes (6.58 +/- 0.12 nmol equiv. leukotriene C4 per g, n = 6) and histamine (10.3 +/- 1.8 of total tissue histamine, n = 5) when challenged with house dust mite extract. 3. Isolated strips of human lung parenchyma, passively sensitized to D. pteronyssinus, contracted when treated with house dust mite extract to a mean value of 40% of the maximal histamine response for each strip. Nedocromil sodium 0.1 and 1 microM inhibited these contractions by 50% and 70% of the control response, but 10 microM had no inhibitory effect. 4. Isolated rings from human bronchus, also passively sensitized to D. pteronyssinus, contracted when treated with house dust mite extract to a mean value of 86% of the maximal histamine response. Nedocromil sodium 1 microM, but not 0.1 or 10 microM, inhibited contractions by 48% of the control response. 5. The therapeutic effects of nedocromil sodium in allergic asthma may depend, partly, on its inhibition of antigen-induced release of leukotrienes and histamine in human lung and its consequent inhibition of antigen-induced contractions of parenchymal and bronchial tissue.
Animals↗
beta-Adrenergic blocking action of halonitrophenethanolamines.
A series of phenethanolamines with N-isopropyl and N-tertbutyl substituents and ring-substituted with nitro- and halogen groups has been prepared. Using guinea-pig isolated atrial and tracheal preparations, the influence of the nitro-group on the beta 1- and beta 2-antagonist actions of the mono-halogen compounds was determined, and the antagonist and partial agonist effects of the halo-nitro-compounds on beta-adrenoceptors in these tissues measured to help elucidate structure-activity relations in this series. The halonitro compounds did not show enhanced activity compared with the mono-halogen substituted analogues. Several of the new compounds showed slight but significant beta 2-antagonist selectivity of action, and one compound was significantly beta 1-selective.
2-Hydroxyphenethylamine↗
Histamine release in exercise-induced asthma.
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Asthma↗
2-Methoxyphenylethanolamines, potential beta-adrenergic blocking agents.
The effect of the introduction of a 2-methoxy substituent on the beta-adrenergic antagonistic properties of a series of 3- and 4-substituted phenylethanolamines (1) was studied. Both the series of bromo- and methyl-substituted compounds behaved similarly, indicating that electronic forces are not significant in determining beta-adrenergic antagonist activity. When compared with the corresponding phenylethanolamines without a 2-methoxy substitutent, the 2-methoxy-4-substituted derivatives (3a and 3d) had enhanced potency and selectivity but the 2,3- (3b and 3e) and the 2,5-disubstitution patterns (3c and 3f) showed a loss of activity. The inconsistent changes in activity prevented any firm conclusions being made about the effect of the ether oxygen and the beta-adrenoceptor antagonistic activity of phenoxypropanolamines.
Adrenergic beta-Antagonists↗
Long-term trial of an alpha adrenoceptor blocking drug (Indoramin) in asthma. A preliminary report.
Eight patients suffering from both asthma and migraine underwent a clinical trial for 3 months of indoramin, an alpha adrenoceptor antagonist with antihistamine and antiserotonin activity. Patients were told indoramin was prescribed for migraine prophylaxis. In three asthmatic patients there was a marked increase in airflow meter (AFM) readings which were recorded daily, the remaining five showing no significant change or a decrease in AFM readings. Indoramin did not appear to potentiate the action of the beta sympathomimetic aerosols. It is suggested that a small population of asthmatic patients may derive therapeutic benefit from an alpha adrenoceptor antagonist. Seven of the eight patients experienced a 50% decrease in the frequency of their migraine headaches.
Adolescent↗
The beta-adrenergic activity of some monosubstituted phenethanolamines.
A series of monosubstituted phenethanolamines with N-isopropyl and N-tert-butyl substituents has been prepared. A detailed pharmacological study has been made of the beta-adrenergic activity of these materials as the nitrogen substituent and the nature and position of the phenyl substituent were changed, and their selectivity has been determined for beta1- and beta2-adrenoceptors in guinea-pig and cat tissues.
Animals↗
Actions of anti-inflammatory drugs on smooth muscle.
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Animals↗
The antagonism by anti-inflammatory analgesics of prostaglandin f 2 alpha-induced contractions of human and rabbit myometrium in vitro.
The anti-inflammatory analgesic drugs, aspirin, indomethacin, phenylbutazone, mefenamic acid ibuprofen and flurbiprofen are shown to inhibit in a dose-dependent manner the force of contraction of isolated human pregnant myometrial strips which have been stimulated to contract by adding prostaglandin (PG) F2alpha to the tissue bath. These drugs and also flufenamic acid and salicin show a similar antagonism of the action of PGF2alpha with isolated rabbit non-pregnant myometrium. The ratio of the inhibitory concentration in vitro to the maximum plasma level after a normal dose in vivo suggests that phenylbutazone and possibly ibuprofen may be capable of inhibiting human uterine contractions in vivo. Patients who were treated with aspirin during induction of abortion using PGF2alpha during the second trimester of pregnancy showed no significant change in the induction-abortion interval compared with patients not taking aspirin.
Abortion, Induced↗
The effects of some bronchodilator and anti-inflammatory drugs on prostaglandin F2alpha-induced contraction of guinea-pig isolated trachea.
1. The bronchodilator drugs isoprenaline, salbutamol, theophylline and prostaglandin E1 (PGE1) relaxed the guinea-pig isolated tracheal chain preparation dose-dependently and their potencies were compared by EC50 values. 2. The non-steroid anti-inflammatory drugs flufenamate, mefenamate and phenylbutazone also relaxed the preparation dose-dependently, but were less potent than the sympathomimetic drugs and PGE1. 3. The contractile response to a submaximal concentration of prostaglandin F2alpha (PGF2alpha) was antagonized by flufenamate, mefenamate, phenylbutazone, aspirin, theophylline, isoprenaline, salbutamol and PGE1, at concentrations similar to or less than the clinical peak plasma levels in man. A relatively higher concentration of indomethacin was required. 4. The antagonism was relatively specific for PGF2alpha in the case of the fenamates, which did not cause comparable reductions in responses to equi-effective concentrations of histamine and carbachol. The other anti-inflammatory drugs, theophylline and the sympathomimetic drugs were less or non-specific. 5. The nature of the shifts in the long dose-response curve for PGF2alpha caused by increasing concentration levels of flufenamate indicates a dual competitive/non-competitive type of antagonism.
Animals↗