Selective Serotonin therapeutic effects

Mechanism of Action An antidepressant and antiobsessive agent that selectively inhibits neuronal reuptake of serotonin. Therapeutic Effect Relieves depression and symptoms of obsessive-compulsive disorder. 

Until the introduction of selective serotonin reuptake inhibitors (SSRIs) in the 1980s, tricyclic antidepressants were the most widely used drugs. The therapeutic effect of amitriptyline and imipramine are related to their ability to inhibit the presynaptic reuptake of both NA and 5-HT. They are referred to as non-selective reuptake inhibitors, whereas many of the other tricyclics are more selective thus, clomipramine is a selective reuptake inhibitor for 5-HT and desipramine and nortriptyline are selective... 

A number of medications used in the treatment of anxiety have effects on serotonin neurotransmission (Ch. 13). These medications include tricyclic antidepressant medications, SSRIs, and monoamine oxidase inhibitors (MAOIs). However, because these medications take weeks to exert their full anxiolytic effects, it is unlikely that blocking the reuptake (and thus increasing synaptic levels) of either serotonin or norepinephrine selectively is responsible for their anxiolytic properties — rather it is suspected that the therapeutic effects are due to changes in gene expression, protein levels, and eventually changes in synaptic connections between neurons. 

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... 

Mechanism of Action A serotonin receptor agonist that binds selectively to vascular receptors, producing a vasoconstrictive effect on cranial blood vessels. Therapeutic Effect Produces relief of migraine headache. 

Mechanism of Action A selective serotonin reuptake inhibitor that blocks the uptake of the neurotransmitter serotonin at CNS presynaptic neuronal membranes, increasing its availability at postsynaptic receptor sites. Therapeutic Effect Relieves depression. 

Mechanism of Action A psychotherapeutic agent that selectively inhibits serotonin uptake in the CNS, enhancing serotonergic function. Therapeutic Effect Relieves depression reduces obsessive-compulsive and bulimic behavior. 

Two types of the MAO enzymes have been found. They are called MAO-A and MAO-B. MAO-A is found in norepinephrine and serotonin synapses, while MAO-B is found in dopamine synapses. Scientists believe that the therapeutic effects of MAOIs are a result of inhibiting MAO-A, while most of the side effects result from actions at MAO-B. The traditional, older MAOIs cannot select which MAO type they affect, so current studies are investigating drugs that might be more selective. 

Although the efficacy of tricyclic antidepressants in the treatment of unipolar depression is beyond reproach, the side-effect profile of these agents makes them less desirable as first-line therapeutic agents. Introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine in the past decade has revolutionized the treatment of depression universally. The side-effect profile of SSRIs, such as nausea, diarrhea and sexual dysfunction, is considerably more benign than that of tricyclic drugs. Multiple controlled trials have proven the efficacy of SSRIs vs. placebo (Nemeroff, 1994). Recently, a number of SNRIs (serotonin and noradrenaline reuptake inhibitors) and so-called atypical antidepressants have been marketed that may have additional advantages over SSRIs, such as more rapid onset of action (venlafaxine. mirtazapine) and low sexual side-effect potential ( bupropion, nefazodone). Additionally, it appears that venlafaxine may be more efficacious in cases of treatment-refractory depression (Clerc et al., 1994 Fatemi et al., 1999). Finally, in a recent report (Thase et al., 2001),... 

Stahl, S.M. (1998) Mechanism of action of serotonin selective reuptake inhibitors serotonin receptors and pathways mediate therapeutic effects and side effects (mechanism of action of SSRIs). Journal of Affective Disorders 12 51(3), 215—35. 

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