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Antidepressants and Receptor Function - Symposium No. 123 by CIBA Foundation Symposium

By CIBA Foundation Symposium

Ciba beginning Symposium 123 Antidepressants and Receptor Function
Chairman: Dennis Murphy, 1986

Depression is a typical and infrequently debilitating affective disease. makes an attempt to boost powerful antidepressants have an extended heritage, yet many questions stay in regards to the mechanisms of motion of such remedies and in regards to the aetiology and pathophysiology of melancholy itself. Early observations concentrated recognition on important monoamine platforms, and animal experiences advised that adjustments in beta-adrenoceptor responsiveness have been a standard impact of antidepressant cures. newer study has encompassed many alternative crucial and peripheral receptors, time-dependent adaptational occasions at synapses, and the sensible importance of alterations in neurotransmitter structures in either people and experimental animals. Such pharmacological reports aimed eventually at elucidating the neurochemical foundation of melancholy and of selling new healing ways, give you the concentration of this symposium quantity. many various equipment of investigating the hyperlinks among monoamine structures, melancholy and antidepressant remedies are defined. contemporary reports of receptors and of monoamine uptake websites within the mind and the outer edge (e.g. in platelets and fibroblasts) are reviewed, with emphasis on alpha and beta adrenoceptors, [3H]imipramine-binding websites and serotonin receptors. the result of tracking amine metabolites in cerebrospinal fluid and of measuring neuroendocrine, physiological and behavioural responses to pharmacological problem are provided, offering info on monoaminergic functionality in depressed sufferers and experimental animals prior to, in the course of and after remedy with antidepressant medicinal drugs or electroconvulsive surprise. Genetic affects on receptor density also are mentioned, as is the relevance to human depressive ailment of animal versions, together with stress-induced behavioural melancholy in rats and responses to social stressors in rhesus monkeys.

This booklet may be of curiosity to neuropharmacologists, psychopharmacologists, scientific pharmacologists, behavioural scientists, psychiatrists and neuroscientists.

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Langer: Our recent study of 17 endogenously depressed patients has the longest wash-out period (Poirier et a1 1986). Some patients had been previously treated with chlomipramine, which inhibits 5-HT uptake, and they were drugfree for four weeks before the study. Others had been given maprotiline or amineptine, which do not modify the density of imipramine-binding sites or alter 5-HT uptake in platelets. These patients were drug-free for at least two weeks beforehand. And seven of the 17 patients studied had been referred to the psychiatric clinic without prior treatment with antidepressants.

Psychopharmacology, in press Raisman R , Sechter D, Briley MS, Zarifian E , Langer SZ 1981 High-affinity 'Himipramine binding in platelets from untreated and treated depressed patients compared to healthy volunteers. Psychopharmacology 75:368-371 Raisman R , Briley MS, Bouchami F, Sechter D, Zarifian E, Langer SZ 1982 'HImipramine binding and serotonin uptake in platelets from untreated depressed patients and control volunteers. Psychopharmacology 77:332-335 Shibata S, Oomura Y, Kita H , Hattori K 1982 Circadian rhythmic changes of neuronal activity in the suprachiasmatic nucleus of the rat hypothalamic slice.

Nevertheless variation may be detectable by more sensitive methods such as peptide mapping after limited proteolysis or two-dimensional electrophoresis. 1986 Antidepressants and receptor function. Wiley, Chichester (Ciba Foundation Symposium 123) y 42-56 The existence of genetic variation in enzymes and other proteins is well established. About 50% of all proteins in human blood show genetic polymorphisms (Nei & Roychoudhury 1982). The same rules may also apply to 42 GENETIC STUDIES AT THE RECEPTOR LEVEL 43 receptor proteins.

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