Biomedical subjects

D S Thomson

Publications and source records attributed to D S Thomson.

7 recordsLinked to original sources

PubMed1992

Computer modelling of glycolipids at membrane surfaces.

Interactions of membrane anchored molecules such as glycolipids with a membrane surface are important in determining headgroup conformation. It is therefore essential to represent these membrane surface interactions in molecular modeling studies of glycolipids and other membrane bound molecules. We introduce here an energy term that represents the interaction of molecules with a membrane bilayer. This membrane interaction energy term has been added to the potential energy function of a molecular dynamics and mechanics program and has been parameterized using partition coefficients between an aqueous solution and a vesicular membrane for two model glycolipids.

Biophysical Phenomena↗

PubMed1992

The aminoquinazoline group as a replacement for the salicylamide group: the design and synthesis of a novel highly selective beta 1 adrenoceptor partial agonist.

The high potency at beta 1 receptors, excellent selectivity (beta 1/beta 2) and high degree of agonism displayed by compounds such as 1 is believed to be due in part to the salicylamide side chain. Two conformations of salicylamide are known to exist in the crystal state (2 and 3), but ab initio calculations suggest that in the absence of crystal packing forces 2 should be more stable. The aminoquinazoline group was judged to be a good replacement for salicylamide in 1, and consequently the oxypropanolamine derivative 4 was prepared. 4 shows extremely high potency at the beta 1 receptor, and excellent beta 1/beta 2 selectivity. It has comparable in vitro activity to 1, although it displays a lower degree of agonism. These results suggest that in this system aminoquinazoline appears to be an excellent mimic of the salicylamide group.

Adrenergic beta-Agonists↗

PubMed1979

An animal model for the investigation of adverse responses to i.v. anesthetic agents and their solvents.

In man the number of adverse responses to the Cremophor-containing anaesthetic agents Althesin and propanidid (Epontol) has been reported to be greater than that encountered with thiopentone. The response of the mini-pig to repeated injection of a range of i.v. anaesthetics and their solvents has been investigated in an attempt to ascertain the possible role of Cremophor in the production of these responses. A second injection of Cremophor EL or the Cremophor/Micellophor-containing agents Althesin and propanidid (Epontol), given 7 days after the first, produced a high frequency of adverse responses. On only one occasion, when alphaxalone and alphadolone were given in a mixture of alcohol and propylene glycol, was an abnormal response seen on the first administration of any agent. The second administration of alphaxalone and alphadolone in the same solvent produced abnormal responses in two of four pigs. No such responses were seen when propanidid was administered in alcohol and propylene glycol or when this solvent mixture was given alone. No abnormal responses were seen following the repeated administration of thiopentone. A marked increase in arterial pressure, and an immediate but transient marked decrease in the numbers of circulating polymorphonuclear leucocytes, were consistent findings in animals showing adverse responses. No abnormal responses were found when the interval between two administrations of Althesin was extended to 3 weeks.

Alfaxalone Alfadolone Mixture↗

PubMed1977

Comparison of selected measures of field dependence.

An examination was made to determine the extent to which the Flexibility of Closure subtest from Hakstian and Cattell's Comprehensive Ability Battery could be substituted for Witkin's Rod-and-frame Test of field dependency. Although the data for 48 subjects (aged 11 to 17 yr.) yielded a significant zero-order correlation between the two tests for females, it was judged insufficient to warrant substitution of the former for the latter test.

Adolescent↗

PubMed1976

The mechansim of tachyphylaxis to ICI 74,917 and disodium cromoglycate.

Pre-incubation in vitro of sensitised peritoneal mast cells for 10 min with either ICI 74,917 (10-5 M) abolished the ability of either drug to inhibit histamine release when subsequently presented to the cells at the same time as antigen. In the case of disodium cromoglycate, tachyphylaxis was abolished by washing the cells after pre-incubation with the drug. The failure to abolish tachyphylaxis to ICI 74,917 was due to the high pre-incubation concentration employed, as at lower concentrations (10-8 M) tachyphylaxis to ICI 74917 was readily abolished by washing. Tachyphylaxis to these anti-allergic agents may be related to a physical blocking of drug receptor sites on or in mast cells.

Animals↗

PubMed1975

Inhibition of immediate hypersensitivity reactions in laboratory animals by a phenanthroline salt (ICI 74,917).

1. The activity of a new anti-allergic compound, I.C.I. 74,917, has been studied in the rat, mouse and guinea-pig. 2. Following intravenous administration, I.C.I. 74,917 inhibits in a dose-dependent manner passive cutaneous anaphylaxis induced in rats and mice by heat-labile homocytotropic antibody. In rats, its potency is approximately 300 times that of disodium cromoglycate. 3. To achieve maximal inhibition, it is necessary to administer I.C.I. 74,917 at the same time as antigenic challenge; dosing before or after challenge has much less effect. 4. Liberation of histamine, provoked by the antigenic challenge of mast cells passively sensitized in vitro by IgE-like antibody, is reduced in the presence of I.C.I. 74,917. 5. Intravenous administration of the compound has no significant effect upon local blueing reactions provoked in the rat by intradermal injection of histamine, 5-hydroxytryptamine or Compound 48/80. It has only a slight effect at high doses upon passive cutaneous anaphylaxis induced in the rat by heat-stable homocytotropic or heterologous (guinea-pig) antibodies. 6. Although not a bronchodilator in the guinea-pig, I.C.I. 74,917 partially inhibits systemic anaphylaxis. A consistent reduction in the severity of antigen-induced bronchospasm was demonstrated in the Konzett-Rossler preparation at doses comparable to those inhibiting passive cutaneous anaphylaxis in the rat. However, there was only slight inhibition of passive cutaneous anaphylaxis in the guinea-pig. 7. I.C.I. 74,917 itself induces bronchospasm when administered to anaesthetized guinea-pigs or to a guinea-pig isolated lung preparation. This effect is reversed by salbutamol, but is not prevented by the prior administration of mepyramine, atropine or methysergide. 8. These results indicate that in the rat, mouse and guinea-pig, I.C.I. 74,917 is a potent inhibitor of certain types of immediate hypersensitivity reactions.

Anaphylaxis↗

PubMed1975

Inhibition of immediate hypersensitivity reactions in the rat by ICI 74,917 and disodium cromoglycate.

ICI 74,917, a potent inhibitor of IgE-mediated passive cutaneous anaphylaxis (PCA) in the rat, exhibited tachyphylaxis in that pre-dosing sensitised rats with a high dose of compound reduced the inhibitory effect on rat PCA of a second dose given at challenge. This phenomenon was most apparent when the pre-dose-challenge dose interval was 15--60 min. Similar findings were obtained using antigen-induced histamine release in vitro from rat peritoneal cells. In these respects, ICI 74,917 was similar to disodium cromoglycate (DSCG) although DSCG appeared less effective in inducing tachyphylaxis than ICI 74,917. There was no evidence in vivo or in vitro that a high dose of either DSCG or ICI 74,917 enhanced the activity of a second low dose of either drug given at challenge.

Animals↗