[Pharmacological approach to the mechanism of potentiation of hypnotics by various monoamine oxidase inhibitors].
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Biomedical subjects
Publications and source records attributed to P Simon.
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Several studies have shown that the noradrenergic system, or more precisely the alpha-adrenergic system, is implicated in the mechanism of action of DPH (Rudzik et al., 1966). In the present study we have demonstrated that prazosin, a relatively specific blocker of post-synaptic alpha-adrenergic receptors, antagonized the anticonvulsant activity of DPH on 3 models of convulsions: convulsions in the quaking mouse, convulsions induced by pentylenetetrazol, convulsions provoked by electroshock. The psychotropic properties of DPH have not been clearly demonstrated in man. It would, therefore, be of interest to perform controlled clinical studies in order to predict possible consequences of treatment in epileptics who are treated at the same time with antagonists of alpha-post-synaptic receptors.
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The aim of the first part of this work is to present the theory of the radioreceptor assay and to compare it to the other techniques of radioanalysis (radioimmunoassay, competitive protein binding assays). The technology of the radioreceptor assay is then presented and its components (preparation of the receptors, radioligand, incubation medium) are described. The analytical characteristics of the radioreceptor assay (specificity, sensitivity, reproducibility, accuracy) and the pharmacological significance of the results are discussed. The second part is devoted to the description of the radioreceptor assays of some pharmacological classes (neuroleptics, tricyclic antidepressants, benzodiazepines, beta-blockers, anticholinergic drugs) and to their use in therapeutic drug monitoring. In conclusion, by their nature, radioreceptor assays are highly sensitive, reliable, precise, accurate and simple to perform. Their chief disadvantage relates to specificity, since any substance having an appreciable affinity to the receptor site will displace the specifically bound radioligand. Paradoxically in some cases, this lack of specificity may be advantageous in that it allows for the detection of not only the apparent compound but of active metabolites and endogenous receptor agonists as well and in that radioreceptors assays can be devised for a whole pharmacological class and not only for one drug as it is the case for classical physico-chemical techniques. For all these reasons future of radioreceptor assay in pharmacology appears promising.