Selective serotonin reuptake inhibitors drug administration

Serendipity has played a major role in the discovery of most classes of psychotropic drugs. For example, the observation that the first antidepressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, impeded the reuptake of biogenic amines into brain slices, or inhibited their metabolism, following their acute administration to rats, provided the experimenter with a mechanism that could be easily investigated in vitro. Such methods led to the development of numerous antidepressants that differed in their potency, and to some extent in their side effects (for example, the selective serotonin reuptake inhibitors) but did little to further the development of novel antidepressants showing greater therapeutic efficacy. The accidental discovery of atypical antidepressants such as mianserin led to the broadening of the basis of the animal models... 

TABLE 22.1 Food and Drug Administration-Approved Indications for Serotonin Reuptake Inhibitor and Selective Serotonin Reuptake Inhibitor Agents... 

FDA, Food and Drug Administration GAD, general anxiety disorder OCD, obsessive-compulsive disorder PMDD, Premenstrual dysphoric disorder PTSD, post-traumatic stress disorder SRI, serotonin reuptake inhibitor SSRI, selective serotonin reuptake inhibitor. 

The selective serotonin reuptake inhibitors (SSRls) have received increased attention in the treatment of anxiety disorders. With the recent Food and Drug Administration (FDA) approval of fluoxetine and fluvoxamine in the treatment of obsessive-compulsive disorder, it has been made clear that this... 

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). ... 

One of the major drawbacks in the pharmacotherapy of depression has been the delay in response of 2-4 weeks between administering an antidepressive drug and the resolution of depression, despite immediate uptake blockade/reduced metabolism of monoamines at a synaptic level. The 5-HTia receptors are a subgroup of G-protein-coupled serotonergic receptors that are present postsynaptically on the soma and dendrites of serotonergic neurons. These receptors are found mainly in the mid and dorsal raphe nuclei of the midbrain and their main effect is inhibitory in nature. It has been demonstrated (mainly in rats) that repeated administration of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants leads to functional desensitization of the somatodendritic 5-HTia... 

The prototypical serotonin reuptake inhibitor (SRI) medication is the non-selective agent clomipramine, a tricyclic antidepressant (TCA). The Selective SRIs (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalo-pram (Celexa). The Food and Drug Administration (FDA) approved clinical indications for these medications are described in Table 22.1. 

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