Pharmacology and Therapeutics - Theses

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Start date: 1960 × End date: 1979 ×

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    Pharmacological aspects of β [beta]-adrenoceptor stimulants
    Malta, Errol ( 1976)
    Summary: Structure-activity relationships of non-catecholamine sympathomimetics have been studied in isolated tissue preparations from the guinea-pig and in anaesthetized cats. The results indicate that the cat most closely resembles man with respect to βr/β 2-receptor selectivity. Investigations show that the subtype of β-adrenoceptor involved in inhibiting antigen-induced histamine release in guinea-pig lung differs from that found in guinea-pig atria and trachea. Hydrocortisone appears to potentiate catecholamine-induced effects in the cat by blocking the extraneuronal uptake mechanisms.
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    The pharmacology of melatonin
    Finnin, Barrie Charles ( 1979)
    Melatonin (N-acetyl-5-methoxytryptamine) causes the pencil fish, Nannostomus beckfordi anomalus, to adopt its nocturnal colour pattern. This action of melatonin has been used to investigate the structural requirements of a 'melatonin receptor'. Of approximately 200 compounds tested melatonin was found to be the most potent. The critical features of the molecule for activity were an indole nucleus with a 5-methoxy substitution and an ethyl-amide side chain at the 3 position. Because the action of melatonin on the pigment cells of the pencil fish is both potent and specific, the pencil fish has been used in a bioassay for melatonin. By means of this bioassay the melatonin content of human pineal glands obtained at autopsy has been determined. Melatonin was not detected in the pineal glands of children younger than four months old. The melatonin content of the gland was found to increase rapidly during the first year of life and after this time there was no statistically significant effect of age on pineal melatonin content, although the few adolescent subjects investigated did show low levels of melatonin. There was no evidence of a diurnal or circadian fluctuation in pineal melatonin content. In order to investigate the possibility of a relationship between pineal melatonin content and the onset of puberty, the pineal melatonin content of female monkeys of various ages was determined. Although monkeys at puberty appeared to show lower melatonin levels than those at other ages the difference was not statistically significant. In an attempt to instrument the bioassay of melatonin and to develop methods for studying receptor interactions, the effects of melatonin were investigated on melanophores of the angelfish, Pterophyllum eimekei, by means of the 'Stripped Fin' technique. Melatonin was found to be a potent inducer of melanosome aggregation and its action was not mediated via α-adrenoceptors. Sensitivity changes to melatonin were observed and the relative potencies of several melatonin-like compounds were determined. There were some differences between the potency ratios observed for angelfish and pencil fish.