Reuptake blocking

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

The answer is that there are two ways in which neurotransmitter levels might be increased. One is to inhibit their destruction after they have been released into the synaptic gap. That is how MAOIs are supposed to work. Recall, however, that after a neurotransmitter is released, some of its molecules are reabsorbed by the presynaptic neuron that released them in a process that is called reuptake . Blocking this reuptake process should also increase the level of neuro transmitters in the brain. In 1961, Julius Axelrod, who later received the Nobel Prize in Medicine for his work on the release and reuptake of neurotransmitters, reported that imipramine, as well as a few other drugs, inhibited the reuptake of norepinephrine in cats. Two years later he reported that these drugs also inhibited the reuptake of serotonin.13... 

SSRIs were developed in an attempt to formulate reuptake-blocking drugs that lacked the troublesome side effects of TCAs. Of the five pharmacological properties of TCAs—blockade of muscarinic receptors, blockade of histamine Hj receptors, blockade of aj-adrenergic receptors, norepinephrine reuptake blockade, and serotonin reuptake inhibition—only the last remains intact in SSRIs. This selectivity has... 

It has been known since the mid-1980s that clomipramine, a potent but nonse-lective serotonin reuptake inhibitor, is effective in reducing OCD symptoms. Since then, numerous studies have confirmed the superiority of clomipramine over placebo in OCD patients, whereas other antidepressant medications with less potent inhibitory effects on serotonin reuptake (e.g., nortripytline, desipramine) seem to be ineffective in OCD. Demonstration of the anti-OCD actions of all five SSRIs, namely, fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram, also supports the hypothesis that the antiobsessional effects of these various pharmacologic agents is due to their potent serotonergic reuptake blocking activity. 

SSRIs can also cause pharmacodynamic drug interactions for some time after withdrawal, through residual serotonin reuptake blocking activity. 

Urinary retention in men over 50 with borderline urine flow has been observed with other agents with potent norepinephrine reuptake blocking properties (e.g., reboxetine, milnacipran), so administer atomoxetine with caution to these patients... 

Theoretically, other agents with norepinephrine reuptake blocking properties, such as venlafaxine, duloxetine, atomoxetine, milnacipran, and reboxetine, could also add to amphetamine s CNS and cardiovascular effects... 

Atypical anti psych otics (with special caution for those agents with monoamine reuptake blocking properties, such as ziprasidone and zotepine)... 

Paroxetine may have mild norepinephrine reuptake blocking actions... 

Sertraline s possible dopamine reuptake blocking properties could contribute to agitation, anxiety, and undesirable activation, especially early in dosing... 

Can cause cognitive and affective flattening , although this could theoretically be diminished in some patients by sertraline s dopamine reuptake blocking properties... 

At very high doses (e.g., >375 mg/day), dopamine reuptake blocked as well in some patients... 

Norepinephrine reuptake blocking actions have theoretical benefits for cognifion (affenfion) and for depression... 

Drug Sedation Muscarinic Receptor Block NE Reuptake Block 5-HT Reuptake Block... 

It is not yet clear whether amantadine blocks uptake of dopamine (or ocher catecholamines) in brain to prolong the useful presence of transmitter. While uptake block of dopamine and norepinephrine has been reported at high amantadine doses, it probably does not play a major role and the evidence of several groups is against it O SS. fhe qtiantitative and qualitative relations must be worked out before the role of reuptake block of catecholamines can be assessed. Snyder suggested that catecholamine uptake blockade (mainly block of dopamine uptake by striatum) may contribute to the mode of action of anticholinergics and antihistamines in antiparkinsonian therapy. 

---