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Biomedical subjects

M S Beer

Publications and source records attributed to M S Beer.

40 records · Page 3Linked to original sources

Pharmacologic exploitation of neurotransmitter receptors for the design of novel antidepressant drugs.

The term 'psychopharmacology' was coined as early as 1920, by David Macht, but it was not until three decades later that the discipline started to develop in a substantial way. The fortuitous discovery of the first antipsychotics and antidepressants, in the 1950s, presented new horizons and gave impetus to the study of drug treatments in psychiatry. In the 1980s, advances in the basic neurosciences, and especially in the characterisation of neurotransmitter receptors, are presenting new opportunities for understanding the biology of mental illness and for designing new drug treatments. This article reviews the evidence linking the action of antidepressant drugs to the regulation of neurotransmitter receptors. We then show how this information has led to a pharmacologic model (melatonin secretion by the human pineal) for the study of antidepressants in depressed patients. Finally, we outline how pharmacologic exploitation of neurotransmitter receptors might lead to new approaches for the design of novel antidepressant drugs.

Animals↗

Effect of conjugated and unconjugated hyperbilirubinaemia on the plasma 25-hydroxy-vitamin D response to ultraviolet radiation in the rat.

1. Vitamin D deficiency was induced in anicteric Wistar rats, Wistar rats before common bile-duct ligation was performed and Gunn rats with unconjugated hyperbilirubinaemia. 2. The effect of ultraviolet radiation on plasma concentrations of 25-hydroxy-vitamin D was studied in a group of control anicteric Wistar rats (n = 11), Wistar rats 8 days after common bile-duct ligation (n = 7) with conjugated hyperbilirubinaemia and in Gunn rats (n = 11). 3. The plasma 25-hydroxy-vitamin D response to ultraviolet radiation was similar in the three groups. 4. It is suggested that neither conjugated nor unconjugated hyperbilirubinaemia prevent cutaneous vitamin D3 synthesis or 25-hydroxylation in the rat.

Animals↗

Differential effects of 5-HT1B/1D receptor agonists on neurogenic dural plasma extravasation and vasodilation in anaesthetized rats.

These studies compared the effects of the 5-HT1B/1D receptor agonists sumatriptan, CP-122 288 ((R)-N-methyl-[3-(1-methyl-2-pyrrolidinylmethyl)-1H-indol-5-yl] methanesulphonamide succinate) and CP-93 129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one dihydrochloride) on neurogenic dural extra-vasation and vasodilation in anaesthetized rats. Dural extravasation, evoked by high intensity (1.2 mA) stimulation of the trigeminal ganglion, was measured using the radioactive plasma marker 125I-labelled bovine serum albumin. Dural vasodilation produced by lower intensity (50-300 microA) stimulation of trigeminal fibres, was measured through a closed cranial window using intravital microscopy. All compounds inhibited dural extravasation (rank order of potency: CP-122 288 > > sumatriptan > CP-93 129) and dural vasodilation (rank order of potency: CP-93 129 > > sumatriptan = CP-122 288). Comparison of the potency of these compounds with their potencies in an in vitro functional model, agonist-induced [35S]GTP gamma S binding, suggests that blockade of dural extravasation was consistent with an action at rat 5-HT1D receptors, but activity at another, unknown, "extravasation receptor" could also be involved. In contrast, inhibition of dural vasodilation was consistent with an action at rat 5-HT1B receptors. We suggest that in our preparations, production of dural vasodilation involves activation of trigeminal A delta-fibres whereas production of dural extravasation involves activation of trigeminal C-fibres. The differential effects of compounds on dural extravasation and vasodilation may therefore be due to the different receptor subtypes involved and to the selective localization of these subtypes on different populations of trigeminal sensory fibre.

Anesthesia, General↗