Biomedical subjects
Publications and source records attributed to D M Temple.
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Indoramin, a drug which blocks alpha-adrenergic, histamine and serotonin receptors, was tested as a protective agent during challenge with bronchoconstrictor agents in guinea-pigs. In conscious guinea-pigs, the time of onset of respiratory distress during continuous administration of aerosolized solutions of histamine, serotonin or ovalbumin (with animals pre-sensitized to this antigen) was measured using a force-displacement transducer applied to the animal's back. This time interval for each guinea-pig was compared with and without indoramin pre-treatment. Indoramin was administered by intraperitoneal injection or by aerosol treatment. In anaesthetized animals under artificial respiration respiratory distress was induced by intravenous injection of histamine and measured by the Konzett-Rössler technique. Indoramin treatment significantly protected guinea-pigs in both types of experiment from the effects of each challenging agent.
A series of new phenylethanolamines with 2-methoxy and/or 4-methyl, 4-chloro, or 4-bromo ring substituents and either N-isopropyl or N-tert butyl substituents have been synthesized and tested for beta 1- and beta 2-adrenoceptor blocking activity using isolated guinea pig atrial and tracheal preparations. Each of the disubstituted N-isopropyl derivatives was a potent antagonist, and the 2-methoxy-4-methyl derivative had a 40-fold beta 1/beta 2-receptor selectivity. Atenolol was shown to have a 32-fold selectivity in the same tests.
A series of 4-bromophenylethanolamines with a variety of amino substituents has been prepared. A detailed pharmacological evaluation has been made of their beta-adrenergic activity to study how the amino substituent may effect the mixed agonist and antagonist action of a phenylethanolamine series.
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.
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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.
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.
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.
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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.
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Explore the source record for details and available documents.