1,721,304 research outputs found
Transynaptic mechanisms in the action of antidepressant drugs
No full textAntidepressant drugs act on different neuronal system and pre- and postsynaptic sites. Integrated transynaptic events are considered to be involved in those adaptive changes which seem to be operative after a prolonged administration. The authors explain how these long-term effects, rather than the acute pharmacological actions, are most likely to represent the biochemical mechanism underlying the delayed onset of antidepressant therapeutic efficacy. Among the possible mechanisms responsible for the adaptation of central aminergic neurons, interactions between serotonergic and noradrenergic systems, chemico-physical properties of the membranes and the modulatory actions of hormones and cotransmitters are considered. © 1984
Rationale for the development of noradrenaline reuptake inhibitors
No full textElucidation of the mechanism of action of antidepressants led to the hypothesis that depression is caused by dysfunction in either the noradrenergic or serotonergic neurotransmitter systems. As inconsistencies in studies designed to confirm this hypothesis arose, the consensus on the biological basis of depression is being refined. The need for better tolerated and effective antidepressants has resulted in the development of agents with more specific receptor binding profiles than the tricyclic antidepressants. These newer antidepressants selectively inhibit the reuptake of noradrenaline (selective NARIs), serotonin (SSRIs) or both (SNRIs). They are useful tools for describing changes in neuroreceptors and intracellular events that occur during antidepressant pharmacotherapy. Reboxetine, a selective NARI, down-regulates beta-adrenergic receptors and desensitises noradrenaline-coupled adenylate cyclase. It also affects cAMP- and Ca2+/calmodulin-dependent phosphorylation systems in a different manner to tricyclic antidepressants and SSRIs. This implies that although different classes of antidepressants may affect common central pathways, the ways in which they do this are distinctive. In conclusion, reboxetine, a selective NARI which is well tolerated and effective in the treatment of depression, has provided us with a new insight into the action of antidepressants and thus will help us to refine our theory of the biological basis of depression.Elucidation of the mechanism of action of antidepressants led to the hypothesis that depression is caused by dysfunction in either the noradrenergic or serotonergic neurotransmitter systems. As inconsistencies in studies designed to confirm this hypothesis arose, the consensus on the biological basis of depression is being refined. The need for better tolerated and effective antidepressants has resulted in the development of agents with more specific receptor binding profiles than the tricyclic antidepressants. These newer antidepressants selectively inhibit the reuptake of noradrenaline (selective NARIs), serotonin (SSRIs) or both (SNRIs). They are useful tools for describing changes in neuroreceptors and intracellular events that occur during antidepressant pharmacotherapy. Reboxetine, a selective NARI, down-regulates β-adrenergic receptors and desensitises noradrenaline-coupled adenylate cyclase. It also affects cAMP- and Ca2+/calmodulin-dependent phosphorylation systems in a different manner to tricyclic antidepressants and SSRIs. This implies that although different classes of antidepressants may affect common central pathways, the ways in which they do this are distinctive. In conclusion, reboxetine, a selective NARI which is well tolerated and effective in the treatment of depression, has provided us with a new insight into the action of antidepressants and thus will help us to refine our theory of the biological basis of depression
Physiology to functionality: The brain and neurotransmitter activity
No full textThe monoamine hypothesis of depression proposes that the biological basis for depression is a deficiency in the neurotransmitters serotonin or noradrenaline, or both. Over the past 30 years this hypothesis has been refined as more experimental and clinical evidence has emerged. The selective serotonin reuptake inhibitors in particular have made a significant contribution to our understanding of the role of serotonin in depression. Our knowledge of the noradrenergic system is less complete, mainly because, until recently, no equivalent agents were available for this system. With the advent of reboxetine, the first selective noradrenaline reuptake inhibitor, attention is again focusing on the role of noradrenaline in depression. To an extent, the action of the selective inhibitors can be predicted through knowledge of the neuroanatomy of the central and peripheral nervous systems. With regard to depression, the most important pathways are those of the serotonergic and noradrenergic neurones projecting to the prefrontal cortex, from the raphe nucleus and locus coeruleus, respectively. However, increasing the levels of the monoamines in the central nervous system affects many other pathways and a wide range of serotonin and adrenergic receptors, leading to a multiplicity of potential beneficial and adverse events. In addition, the complex intracellular responses are beginning to be examined, again with the aid of the selective antidepressants
Ontogenetic study of [3H]imipramine binding sites and serotonin uptake system: Indication of possible interdependence
No full textMolecular biology of dopaminergic receptors: Pharmacological implications
No full textMolecular biology techniques have had a tremendous impact on the studies of neurotransmitter receptors, in particular of dopamine receptors. Until recently only two dopamine receptors were described on the basis of pharmacological and biochemical experiments: the D1 and D2 receptors, differently coupled to adenyl cyclase and other second messenger systems. Molecular cloning studies have revealed the existence of five functional dopamine receptors. Several studies have been conducted regarding the distribution of these different receptor mRNAs and the expression of dopamine receptors in transfected cell lines in order to better understand the functional significance of the individual receptors. At present, little is known about the physiological and pharmacological importance of this receptor heterogeneity. Future reseach should allow us to get a better insight in the physical structure of these receptors in order to prepare highly selective dopaminergic ligands to use in the therapies related to dysfunction of the dopaminergic system. In fact this heterogeneity gives the possibility for developing selective antagonists for use in clinical therapeutics. Recently clinical studies have been focused on drugs like clozapine and risperidone which can modulate not only dopamine receptors but also serotonergic receptors (5HT2) having less extrapyramidal side effects characteristic of the blockage of D2 receptors
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