54 There was also no relationship to genetic variants of the NF: transporter.55 Neurotransmitter receptors In addition to monoamine deficiency, an abnormality in transmission can also arise from changes in receptor function, which means either changes in coupling between transmitters and receptors or changes in the downstream signal transduction cascade. For both the noradrenergic and serotonergic system, a multiplicity of receptors have been identified so far, each classified check details according to its pharmacological or molecular characteristics. NE transmission Inhibitors,research,lifescience,medical is regulated
via α- or β-adrenoccptors and their various subtypes, with the same pharmacological properties in brain and periphery.29 Receptor classification for the serotonergic Inhibitors,research,lifescience,medical system has proceeded rapidly and to date we know of several major categories, ranging from 5-HT1 to 5-HT7 receptors, each with further subtypes.56 Receptors are not static entities: their numbers and affinities are regulated by many factors, for example, the transmitter concentration, which leads to
compensatory down- or upregulation in the receptor protein. Despite Inhibitors,research,lifescience,medical intensive investigation over the years, our knowledge of alterations in monoamine receptor numbers or affinities in untreated depressed patients is relatively poor and unconvincing. The frequently reported supersensitivity of presynaptic α2 -adrenoceptors, which modulate the release of NE,42 as well as altered numbers and affinities of 5-HT1 and 5-HT2 receptors in brain and/or platelets57 have been the subject of much discussion. Due to the rapid Inhibitors,research,lifescience,medical development of molecular biology, interest has shifted from the mere determination of the receptor numbers or affinities toward the signal transduction cascade. There is mounting
evidence Inhibitors,research,lifescience,medical for the role of these mechanisms in the modulation of neuronal activity and pathophysiology of mental disorders.58 Using this new approach, several studies in peripheral cell model systems and/or in postmortem brain tissue report alterations in G-proteins,59 at multiple sites of the cAMP pathway,60 and in protein kinases.61 These findings have led to the formulation of a molecular and cellular hypothesis of depression, which proposes that signal transduction pathways are in a pivotal position in SB-3CT the CNS, in that they affect the functional balance between multiple neurotransmitter systems and physiological processes. Pharmacological treatment of depression Since Kuhn introduced imipramine in the 1950s, the availability of antidepressant drugs has expanded greatly, not only in terms of number, but also, and especially, in terms of diversity in the associated pharmacological effects. The first-generation antidepressants, the tricyclic antidepressants (TCAs) and MAO inhibitors (MAOIs), increase the concentrations of 5-HT and/or NE and are effective in alleviating the symptoms of depression.