Serotonin neuronal reuptake

The TCAs have affinity for both receptors and transporters of monoamine transmitters and behave as antagonists in both respects. Thus, the neuronal reuptake of norepinephrine (p. 82) and serotonin (p. 116) is inhibited, with a resultant increase in activity. Muscarinic acetylcholine receptors, a-adrenocep-tors, and certain 5-HT and hista-mine(Hi) receptors are blocked. Interference with the dopamine system is relatively minor. 

It is believed that tricyclic antidepressants inhibit the (neuronal) reuptake of norepinephrine (noradrenaline) and/or serotonin by presynaptic nerve endings, thus blocking one of the leading mechanisms of their inactivation, and thereby increasing the concentration of the indicated amines potentiating their effects. It should be noted that, as a rule, secondary amines, which are representatives of tricyclic antidepressants, exhibit high activity, blocking the neuronal reuptake of norepinephrine, while tertiary amines act more on the neuronal reuptake of serotonin. 

Fluoxetine is a phenylpropylamine that inhibits the neuronal reuptake of serotonin, which presumably has a direct relationship on antidepressant activity. This compound has either... 

It is believed that trazodone, in therapeutic doses, inhibits the neuronal reuptake of serotonin. It is not a MAO inhibitor or a CNS stimulator. It has a minor influence on the reuptake of norepinephrine and dopamine. In addition, it does not bind with cholinergic or a-adrenergic receptors. Synonyms of this drag are thrombran, pragmarel, desyrel, and others. 

Serotonin syndrome Some TCAs inhibit neuronal reuptake of serotonin and can increase synaptic serotonin levels (eg, clomipramine, amitriptyline). Either therapeutic or excessive doses of these drugs, in combination with other drugs that also increase synaptic serotonin levels (such as MAOIs), can cause a serotonin syndrome consisting of tremor, agitation, delirium, rigidity, myoclonus, hyperthermia, and obtundation. 

Pharmacology These agents are potent and selective inhibitors of neuronal serotonin reuptake and they also have a weak effect on norepinephrine and dopamine neuronal reuptake. 

Which of the following antidepressants is most selective for inhibition of neuronal reuptake of serotonin ... 

Imipramine is a TCA with mixed serotonin and norepinephrine properties. Sertraline belongs to the class of antidepressants know as the SSRIs and selectively blocks neuronal reuptake of serotonin. 

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. 

The delay in onset of anxiolytic and antipanic effects of serotonin reuptake inhibitors and related compounds is still an issue of much speculation. It appears paradoxical that serotonin reuptake inhibitors block serotonin uptake immediately, whereas it takes weeks before their therapeutic effects become apparent. Recently, the idea was advanced that the tentative enhanced serotonin neurotransmission caused by short-term administration of serotonin reuptake inhibitors is offset by negative feedback in the raphe nuclei (Artigas 1993 Blier and de Montigny 1994). The increased level of serotonin in the somatodendritic area, resulting from serotonin uptake inhibition, reduces serotonin neuronal firing through activation of the 5-HTj, autoreceptors. Alterations in the feedback regulation upon repeated administration may... 

The mechanism by which bupropion acts as an aid in smoking cessation is unknown. Bupropion weakly inhibits neuronal reuptake of noradrenaline and serotonin and inhibits the reuptake of... 

Of the clinically tested new antipsychotics, ziprasidone has the highest 5-HT2A/D2 receptor-affinity ratio. Ziprasidone is an antagonist at the a -adrenoreceptor, but its affinity is half that of its D 2 affinity. In addition, compared with its affinity for D 2 and 5-HT2A receptors, ziprasidone has a relatively low affinity for histamine receptors (pKJ = 7.33). In vitro, ziprasidone is a moderately potent inhibitor of neuronal reuptake of norepinephrine, serotonin, and, to a lesser extent, dopamine. This property is shared with some antidepressants, and contrasts with risperidone, which is inactive at all three monoamine uptake sites. 

FIGURE 6-35. Mechanism of action of serotonin selective reuptake inhibitors (SSRIs)—part 1. Depicted here is a serotonin neuron in a depressed patient. In depression, the serotonin neuron is conceptualized as having a relative deficiency of the neurotransmitter serotonin. Also, the number of serotonin receptors is up-regulated, or increased, including presynaptic autoreceptors as well as postsynaptic receptors. 

FIGURE 6-36. Mechanism of action of serotonin selective reuptake inhibitors (SSRls)—part 2. When an SSRI is administered, it immediately blocks the serotonin reuptake pump (see icon of an SSRI drug capsule blocking the reuptake pump). However, this causes serotonin to increase initially only in the somatodendritic area of the serotonin neuron (left) and not in the axon terminals (right). 

FIGURE 6-37. Mechanism of action of serotonin selective reuptake inhibitors (SSRIs)—part 3. The consequence of serotonin increasing in the somatodentritic area of the serotonin neuron, as depicted in the Figure 6-36, is to cause the somatodendritic serotonin 1A autoreceptors to desensitize or down-regulate (red circle). 

FIGURE 6-39. Mechanism of action of serotonin selective reuptake inhibitors (SSRIs)—part 5. Finally, once the SSRIs have blocked the reuptake pump (Fig. 6-36), increased somatodendritic serotonin (Fig. 6-36), desensitized somatodendritic serotonin 1A autoreceptors (Fig. 6—37), turned on neuronal impulse flow (Fig. 6-38), and increased release of serotonin from axon terminals (Fig. 6— 38), the final step shown here may be the desensitization of postsynaptic serotonin receptors. This has also been shown in previous figures demonstrating the actions of monoamine oxidase (MAO) inhibitors (Fig. 6-4) and the actions of tricyclic antidepressants (Fig. 6—6). This desensitization may mediate the reduction of side effects of SSRIs as tolerance develops. 

Sibutramine inhibits neuronal reuptake of NE and serotonin (similarly to antidepressants, p. 226). It diminishes appetite and is classified as an antiobesity agent (p.328). 

Citalopram is a racemic bicyclic phthalane derivative and is a highly selective serotonin re-uptake inhibitor with minimal effects on noradrenaline and dopamine neuronal reuptake. Inhibition of 5-HT re-uptake by citalopram is primarily due to escitalopram, the active S-enantiomer of citalopram (1). One would expect escitalopram to be twice as potent as citalopram but otherwise not to differ significantly from the racemic mixture. However, escitalopram is marketed as being more efficacious than citalopram because, it is argued, the inactive R-isomer present in the racemate actually inhibits binding of the S-enantiomer to its site of action, the serotonin transporter. In some, but not all, clinical trials escitalopram has been statistically superior to citalopram in terms of speed of onset of therapeutic action and improvement on depression rating scales. The clinical significance of these differences is debatable (2). 

Selective serotonin reuptake inhibitors (SSRIs) inhibit the neuronal reuptake of serotonin in the central nervous system and have shown mixed efficacy in the treatment of autistic symptoms (Moore et al., 2004). A number of studies have shown reductions in repetitive behaviors, lethargy, inappropriate speech, and improvements in the ability to relate to others, cognition, language improvement with fluoxetine (DeLong et al., 1998 Fatemi et al., 1998 Peral et al., 1999), fluvoxamine (McDougle et al., 1996b), and sertraline (Steingard et al., 1997). However, other studies have shown a lack of response with fluvoxamine (Martin et al., 2003) and citalopram (Couturier and Nicolson, 2002). 

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