Monoamine receptors antagonists

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

Azolides used as inhibitors for monoamine oxidase1171 or human leucocyte elastase,1181 as inductors of recessive lethal genes in Drosophila,1191 as histamine H2-receptor antagonists,1201 as anti-ulcer agents,1211 or as pharmacophores for anthelmintic, analgesic, and antimicrobial activity 1221... 

Two general classes of alkaloids are distinguished in ergot amine alkaloids and amino acid alkaloids (table 5.9) (Peroutka 1996). While the amine alkaloids are selective for antagonist effects on serotonin receptors, the amino acid alkaloids are less selective and act upon other monoamine receptors. The constituents of interest for cognitive enhancement are predominantly the amine alkaloids. 

This model detects both agonists and antagonists at monoamine receptors. 

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. 

Several different types of serotonin receptor (for example, S-HTi / 5-HT2A/ 5-HT2C/ 5-HTib/id) have been associated with the motor side effects of the SSRIs which may arise should these drugs be administered in conjunction with a monoamine oxidase inhibitor. The 5-HT3 receptor is an example of a non-selective cation charmel receptor which is permeable to both sodium and potassium ions and, because both calcium and magnesium ions can modulate its activity, the 5-HT3 receptor resembles the glutamate-NMDA receptor. Antagonists of the 5-HT3 receptor, such as ondansetron, are effective antiemetics and are particularly useful when... 

The 5-H T3 receptor is the only monoamine receptor coupled to an ion channel, probably a Ca " channel. It is found in the cortex, hippocampus, and area postrema. It is typically localized presynaptically and regulates neurotransmitter release. Well-known antagonists are the potent antiemetics ondansetron and granisetron. 

Considerable attention has been paid to the ultimate postsynaptic effects of increased neurotransmitters in the synapses. In tests of postsynaptic effects, cAMP concentrations have consistently decreased rather than increased, in spite of the presumably longer duration of action of the transmitters. In addition, the number of postsynaptic -adrenoceptors has shown a measurable decrease that follows the same delayed time course as clinical improvement in patients. Thus, the initial increase in neurotransmitter seen with some antidepressants appears to produce, over time, a compensatory decrease in receptor activity, ie, down-regulation of receptors. Decreases in norepinephrine-stimulated cAMP and in B-adrenoceptor binding have been conclusively shown for selective norepinephrine uptake inhibitors, those with mixed action on norepinephrine and serotonin, monoamine oxidase inhibitors, and even electroconvulsive therapy. Such changes do not consistently occur after the selective serotonin uptake inhibitors, 2 receptor antagonists, and mixed serotonin antagonists. 

The oxazolidinone-based compounds are the most common (Figure 23.1), and examples include antibacterial,27-28 adhesion receptor antagonists,29-30 tumor necrosis factor inhibitors,31 platelet aggregation inhibitors,32 antimigraine drugs,33 and monoamine oxidase inhibitors.3435 In one case, an oxazolidinone has been used as a transdermal drug delivery agent.36... 

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