Antidepressants receptor specificity

Relative receptor specificity of some antidepressant drugs. 

Norepinephrine Mostly excitatory, but inhibitory in some areas. Secreted by neurons in the locus ceruleus (subcortical area) to widespread areas of the brain, controlling wakefulness, overall activity, and mood. Also diffusely secreted in the sympathetic nervous system. Diffuse and widespread symptoms, including depression, changes in blood pressure, heart rate, and diffuse physiological responses, among many others. An important transmitter in the sympathetic branch of the autonomic nervous system. Diffusely affected by many medications. Several antidepressants work specifically on this neurotransmitter and its receptor sites. Many medications for general medical conditions affect this neurotransmitter as well. 

Serotonin Usually inhibitory helps control mood, influences sleep, and inhibits pain pathways in the spinal cord. Secreted by subcortical structures into hypothalamus, brain, and spinal cord. There are many subtypes of serotonin receptors. Diffuse and widespread symptoms depression, headache, diarrhea, constipation, sexual dysfunction, and other medical symptoms. The selective serotonin reuptake inhibitors (SSRIs), the most commonly used antidepressants, work specifically on this neurotransmitter system. 

Future Outlook for Antidepressants. Third-generation antidepressants are expected to combine superior efficacy and improved safety, but are unlikely to reduce the onset of therapeutic action in depressed patients (179). Many dmgs in clinical development as antidepressive agents focus on estabhshed properties such as inhibition of serotonin, dopamine, and/or noradrenaline reuptake, agonistic or antagonistic action at various serotonin receptor subtypes, presynaptic tt2-adrenoceptor antagonism, or specific monoamine—oxidase type A inhibition. Examples include buspirone (3) (only... 

Older tricyclic antidepressants are set in italics. The specificity of action of tricyclic antidepressants (in particular of amitritpyline, imipmmine, doxepine, noitriptyline, maprotiline) is limited because at therapeutic levels ihese drugs also block receptors (H t-histamine, a,-adrenergic, muscarinic). 

There is another reason why medications exert multiple effects. For example, an antidepressant that very specifically promotes serotonin neurotransmission and has little or no interaction with other receptor types will still produce multiple effects. How can this be Remember that in different areas of the brain, a single neurotransmitter can assume very distinct roles. When an individual takes a medication that alters the activity of a particular neurotransmitter, it generally does so throughout the brain. Consequently, the dopamine receptor blocking effect of haloperidol (Haldol) reduces hallucinations and paranoia in one brain region but causes upper extremity stiffness through its action in another brain region. 

Listing of antidepressants grouped by principal mechanism of action in the synapse. Abbreviations MAOI—irreversible = irreversible monoamine oxidase inhibitor MAOI—reversible = reversible monoamine oxidase inhibitor NDRl = norepinephrine/ dopamine reuptake inhibitor NRI = norepinephrine reuptake inhibitor NSRl = norepinephrine/serotonin reuptake inhibitor NSSA = norepinephrine/specific serotonin agonist SRI = serotonin reuptake inhibitor SRl/serotonin-2 blocker = serotonin reuptake inhibitor and serotonin-2 receptor antagonist. 

Mirtazapine (Remeron). Mirtazapine is the newest of the atypical antidepressants. It mainly works by blocking the alpha-2 negative feedback receptor and thus increases norepinephrine and serotonin activity. In addition, mirtazapine blocks serotonin-2 and serotonin-3 receptors to produce a specific serotonin action like nefazodone. Mirtazapine is approved for the treatment of depression. Its use in the anxiety disorders is being studied. 

Buspirone (Buspar). The first nonsedating, nonbenzodiazepine specifically introduced as an anxiolytic, buspirone is FDA approved for the treatment of GAD. This medication acts as a partial agonist at the postsynaptic serotonin (5HT)-1A receptor. Like the antidepressants, buspirone has a delayed onset of action and effectively relieves the intrapsychic symptoms of GAD. Devoid of the muscle-relaxing properties of benzodiazepines, buspirone does not as effectively relieve the physical symptoms of GAD. Buspirone is not effective in the treatment of depression. Furthermore, its utility for the treatment of anxiety disorders other than GAD appears to be limited. 

In SUMMARY, irrespective of the specificity of the antidepressants following their acute administration, it can be speculated that a common feature of all these drugs is to correct the abnormality in neurotransmitter receptor function. Such an effect of chronic antidepressant treatment may parallel the time of onset of the therapeutic response and contribute to the receptor sensitivity hypothesis of depression and the common mode of action of antidepressants. 

There are several mechanisms whereby antidepressants can modify intracellular events that occur proximal to the posts)maptic receptor sites. Most attention has been paid to the actions of antidepressants on those pathways that are controlled by receptor-coupled second messengers (such as cyclic AMP, inositol triphosphate, nitric oxide and calcium binding). However, it is also possible that chronic antidepressant treatment may affect those pathways that involve receptor interactions with protein tyrosine kinases, by increasing specific growth factor synthesis or by regulating the activity of proinflammatory cytokines. These pathways are particularly important because they control many aspects of neuronal function that ultimately underlie the ability of the brain to adapt and respond to pharmacological and environmental stimuli. One mechanism whereby antidepressants could increase the s)mthesis of trophic factors is... 

Known as a noradrenaline and specific serotonin antidepressant (NaSSA). More potent affinity for alpha-2 adrenoceptors and 5-HT receptors than mianserin HI antagonist... 

In humans, the antidepressant activity of NMDA receptor antagonists has not been evaluated extensively (Skohiick 1999). In animal models of depression, NMDA receptor antagonists have been reported to exert positive effects in most studies (Trullas 1997). This concerns mainly the forced swim test (Maj 1992 Moryl et al. 1993 PrzegaUnski et al. 1997) and stress-induced anhe-donia (Papp and Moryl 1994). Amantadine but not memantine was effective against reserpine-induced hypothermia (Moryl et al. 1993). In the forced swim test, both amino-adamantanes produced specific antidepressive-like activity (Moryl et al. 1993). 

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