Selective serotonin reuptake inhibitors structure

Schuldiner, S (1998) Vesicular neurotransmitter transporters. In Neurotransmitter Transporters Structure, Function, and Regulation (Ed. Reith, MEA), Humana Press, Totowa, NJ, pp. 215-240. Stanford, SC (1995) Central noradrenergic neurones and stress. Pharmac. Ther. 68 297-342. Stanford, SC (1999) SSRI-induced changes in catecholaminergic transmission. In Selective Serotonin Reuptake Inhibitors (SSRIs) Past, Present and Future (Ed. Stanford, SC), RG Landes Co., Austin, TX, pp. 147-170. 

Figure 20.5 The chemical structure of the selective serotonin reuptake inhibitors (SSRIs)...

Some failures will be due to the presence of variants in drug handling. Patients who are rapid acetylators of isoniazid have a slower antituberculous response than slow acetylators (Evans and Clarke, 1961). Asthmatics who do not respond well to (32-agonist bronchodilators may have fewer functioning p2-adrenergic receptors (Drysdale et al., 2000). Variations in the synthesis or structure of the serotonin transporter protein, which is involved in selective reuptake of serotonin by presynaptic neurons, may explain why some patients with depressive disorders respond to selective serotonin reuptake inhibitors and others do not (Steimer et al., 2001). 

Selective serotonin reuptake Inhibitors (SSRIs) and other newer antidepressants Due to their widely differing structures in comparison to TCAs, several methods for their determination in biological matrices have been developed for each compound individually. Presented here are examples of HPLC determinations for several of these drugs. 

Structure is also essential in complex biological molecules. A lot of medicines used for psychiatric illnesses such as depression rely on their ability to interact with certain proteins in the brain. For instance, a class of antidepressants—medications that alleviate the symptoms of depression—act on proteins involved with the collection (reuptake) of the chemical serotonin, and they are known as selective serotonin reuptake inhibitors (SSRIs). This class of antidepressants includes Prozac and Zoloft. Earlier medications were also effective and are still sometimes used though they produce a number of side effects, such as dietary problems. Although an SSRI can also generate potentially dangerous side effects, psychiatrists tend to observe these effects less often. (Brain chemistry is the subject of chapter 3.)... 

Structures of several selective serotonin reuptake inhibitors. 

Antidepressants generally fall into one of three categories (1) tricyclic antidepressants (TCAs), which are so named because of their three-ring chemical structure (2) selective serotonin reuptake inhibitors (SSRIs), which block only the reabsorption of serotonin and not of norepinephrine and (3) monoamine oxidase (MAO) inhibitors, which inhibit the metabolic breakdown of norepinephrine and/or serotonin. 

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. 

Once armed with this understanding, pharmaceutical researchers went back to their labs and developed molecules capable of replicating these effects. Adjusting the structure of the molecules and submitting these new compounds to various tests, they produced the second generation antidepressants, the SSRIs (selective serotonin reuptake inhibitors as their name indicates, they selectively inhibit the reuptake of serotonin from the synapse back into the neuron from which it was originally released) and several others. 

At least several weeks administration of virtually all antidepressant drugs, be they the classical tricyclic compounds or the newer selective serotonin reuptake inhibitors (SSRI), is required before patients see relief from their symptoms. A recently developed SSRI whose structure departs markedly from existing agents appears to differ from other agents, in that it appears to act in a much shorter time. The final step in the synthesis of this agent elzasonan (182) comprises aldol condensation of the benz-aldehyde (180) with the thiamorpholine (181). ... 

Heterocyclics (second- and third-generation antidepressants) Drugs of varied chemical structures several have actions different from those of tricyclic antidepressants or selective serotonin reuptake inhibitors... 

Serotonin Norepinephrine Reuptake Inhibitor Selective Serotonin Reuptake Inhibitor Sales of Mevalotin (Daiichi Sankyo, 799M) not included Sales of Amlodin (Sumitomo, 506M) not included Note Salts have been omitted from structures. 

Figure 11 Structures of the more active enantiomers of selective serotonin reuptake inhibitors (SSRI).

Atomoxetine (Straterra , originally tomoxetine or tomoxetin, 3) was first described and synthesized by chemists at Eli Lilly in the late 1970s and was one of the few compounds that was known to display meaningful selectivity for the norepinephrine reuptake transporter (NET) versus the serotonin reuptake transporter (SERT) and the dopamine reuptake transporter (DAT) (Barnett, 1986 Molloy and Schmiegel, 1997). Atomoxetine was one of several structurally related and commercially successful monoamine reuptake inhibitors that were developed by Lilly for the treatment of various psychiatric disorders (Eig. 17.4). Fluoxetine (43) and duloxetine (44) have both gained approval in the United States as Prozac and Cymbalta , respectively, and nisoxetine (45) is widely used as a tool in biology. 

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