Inhibition serotonin reuptake

Monoamine oxidase inhibition Serotonin reuptake inhibition Norepinephrine reuptake inhibition Dopamine reuptake inhibition a2-Adrenergic receptor blockade Serotonin-2A receptor blockade Serotonin-2C receptor blockade Serotonin-3 receptor blockade op-Adrenergic receptor blockade Histamine-1 receptor blockade Muscarinic cholinergic receptor blockade... 

Clomipramine A tricyclic antidepressant that selectively inhibits serotonin reuptake into the presynaptic neuron. 

Serotonin syndrome (sibutramine) The rare, but serious, constellation of symptoms also has been reported with the concomitant use of selective serotonin reuptake inhibitors and agents for migraine therapy (eg, sumatriptan, dihydroergotamine), certain opioids (eg, dextromethorphan, meperidine, pentazocine, fentanyl), lithium, or tryptophan. Because sibutramine inhibits serotonin reuptake, it should not be administered with other serotonergic agents. 

Enhances Serotonin Synthesis Increases Serotonin Release Serotonin agonist Inhibits Serotonin Catabolism Inhibits Serotonin Reuptake... 

Tramadol has about one tenth the pain-relieving ability of morphine.53 There are two enantiomers, and both contribute to pain relief, but via different mechanisms. (+)-Tramadol and the metabolite (+)-0-desmethy 1-tramadol, which is referred to as Ml, are agonists of the mu opioid receptor. (+)-Tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine re uptake.25 This latter action enhances the inhibitory effects on pain transmission in the spinal cord. Because the actions of the two enantiomers are complementary, they are usually supplied as a racemic mixture. However, because it is a serotonin-reuptake blocker, interaction with other medications can lead to the occurrence of serotonin syndrome.54... 

Although by definition, all SSRI antidepressants are believed to inhibit serotonin reuptake, they also have a variety of effects on other neurotransmitter systems. Fluoxetine, for example, has been shown to decrease brain dopamine levels in some animal studies (Smith et al. 2000). They also differ from each other in their profiles of action on different systems. 

The selective serotonin-reuptake inhibitors (SSRI) are a new group of chemically unique antidepressant drugs that specifically inhibit serotonin reuptake (see Figure 12.3). This contrasts with the tricyclic antidepressants that nonselectively inhibit the uptake of norepinephrine, and serotonin, and block muscarinic, H histaminic and a -adrenergic receptors. Compared with tricyclic antidepressants, the SSRIs cause fewer anticholinergic effects and lower cardiotoxicity. However, the newer serotonin reuptake inhibitors should be used cautiously until their long-term effects have been evaluated. 

Tropane derivatives, (V), prepared by Kozikowski (5) were highly selective as dopamine transporters as well as for selectively inhibiting serotonin reuptake and/or norepinephrine and used in the treatment of psychiatric and neurodegenerative disorders. 

The single and multiple-dose pharmacokinetics of citalopram are linear and dose-proportional in the range 10-60 mg/day. Citalopram is metabolized to demethylcitalo-pram, didemethylcitalopram, citalopram-N-oxide, and a deaminated propionic acid derivative. Citalopram has a mean half-life of about 35 hours (4). Racemic citalopram is several times more potent than its metabolites in inhibiting serotonin reuptake (5). 

If patient Is taking any agent that can Inhibit serotonin reuptake (e.g., SSRIs, sibutramlne, tramadol, mllnacipran, duloxetine, venlafaxine, clomipramine, etc.)... 

Sertraline and fluoxetine undergo metabolic demethylation. Unlike the metabolites of most other SSRIs, the desmethyl metabolite of fluoxetine, norfluoxetine(34), retains the ability to inhibit serotonin reuptake (205). Hence, fluoxetine takes longer to achieve steady-state levels, and it retains activity after metabolism. The half-life of fluoxetine is approximately 1 day, but elimination of norfluoxetine is prolonged (7-15 days) (205). In addition to its actions as an SSRI, norfluoxetine also binds at 5-HT, receptors (127). 

Each SSRI has its own unique abilities to alter brain chemistry, in addition to their main effect of inhibiting serotonin reuptake. Prozac (Figure 3.4), for instance, lasts up to twice as long as Zoloft or Paxil. This means more time would be... 

Trazodone (150 mg/day) is indicated in the treatment of depression. Trazodone selectively inhibits serotonin reuptake in the brain, causes beta-receptor subsensitivity, and induces significant changes in serotonin-receptor binding with only a slight effect on alpha-adrenergic receptors. Also, trazodone potentiates the action of 5-hydroxytryp-tophan, the precursor of serotonin (see also Tables 5 through 7). 

Indalpine is a non-tricyclic antidepressant with a serotonin selective profile. It is 6-7 times more potent than fluoxetine and clomipramine in inhibiting serotonin reuptake m vitro in rat brain synaptosomes. Statistically significant clinical effects within one week of onset of treatment have been reported. An anxiolytic effect may accompany the antidepressant effect. Indalpine appears devoid of anticholinergic and cardiovascular side effects and does not promote weight gain or affect appetite. 

There are no reports of adverse reactions between sibutramine and the MAOIs. However, sibutramine inhibits serotonin reuptake, and because the serious serotonin syndrome can occur when MAOIs and SSRIs are used together, the manufacturers warn that concurrent use of sibutramine and MAOIs is contraindicated. They say that 14 days should elapse between stopping either drug and starting the other. The US manufacturers included selegUine in this warning. ... 

Serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g. duloxetine, venlafaxine and desvenlafax-ine) inhibit the reuptake of both serotonin and norepinephrine and are referred to as dual inhibitors or selective serotonin norepinephrine inhibitors . The SNRIs lack of anticholinergic side effects results in a distinct advantage over traditional TCAs [13,77,78]. For example, duloxetine is a potent, balanced inhibitor of serotonin and norepinephrine reuptake [79]. Venlafaxine inhibits serotonin reuptake at lower dosages and inhibits both serotonin and norepinephrine reuptake at higher dosages [70,80]. 

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