Reboxetine receptors

Many neurotransmitters are inactivated by a combination of enzymic and non-enzymic methods. The monoamines - dopamine, noradrenaline and serotonin (5-HT) - are actively transported back from the synaptic cleft into the cytoplasm of the presynaptic neuron. This process utilises specialised proteins called transporters, or carriers. The monoamine binds to the transporter and is then carried across the plasma membrane it is thus transported back into the cellular cytoplasm. A number of psychotropic drugs selectively or non-selectively inhibit this reuptake process. They compete with the monoamines for the available binding sites on the transporter, so slowing the removal of the neurotransmitter from the synaptic cleft. The overall result is prolonged stimulation of the receptor. The tricyclic antidepressant imipramine inhibits the transport of both noradrenaline and 5-HT. While the selective noradrenaline reuptake inhibitor reboxetine and the selective serotonin reuptake inhibitor fluoxetine block the noradrenaline transporter (NAT) and serotonin transporter (SERT), respectively. Cocaine non-selectively blocks both the NAT and dopamine transporter (DAT) whereas the smoking cessation facilitator and antidepressant bupropion is a more selective DAT inhibitor. 

Examples maprotiline a bridged" tricyclic with affinity for histamine, HI, and alpha-1 adrenoceptors. Causes seizures reboxetine not cardiotoxic does not have an affinity for any neurotransmitter receptors... 

Reboxetine is the only selective and reasonably potent noradrenaline reuptake inhibitor available clinically at the present time. Reboxetine has a chemical structure not dissimilar from viloxazine, an antidepressant which was of only limited clinical interest in the 1970s because of its weak efficacy and unacceptable side effects (nausea, vomiting and occasionally seizures). Unlike the secondary amine TCA antidepressants, such as maprotiline, desipramine, nortriptyline and protriptyline, reboxetine does not affect any other transporter or receptor system and therefore is largely devoid of TCA and SSRI-like side effects. In clinical trials, reboxetine has been shown to be as effective as the SSRIs in the... 

Reboxetine achieves its antidepressant effect through selective inhibition of norepinephrine reuptake. Rebox-etine s receptor occupancy profile shows little or no af-... 

It has low affinity for adrenergic, cholinergic, histaminic, dopaminergic, and serotoninergic receptors ( 176). At a dose of 4 mg twice daily, reboxetine has exerted substantial inhibition of NE uptake in humans as witnessed by abolishment of the tyramine pressor response ( 177). 

In terms of comparative adverse effects, imipramine produces more dry mouth than reboxetine probably because imipramine blocks muscarinic cholinergic receptors as well as inhibiting NE uptake (47,5). Imipramine also produces more tremulousness and hypotension than reboxetine. Consistent with their pharmacology, fluoxetine produces more serotonin-mediated adverse effects than does reboxetine (i.e., nausea, loose stools, and somnolence), whereas reboxetine causes more sympathomimetic adverse effects (476). To date, reboxetine has not been reported to cause an increased incidence of laboratory abnormalities. 

When reboxetine was substituted for doxepin the cholesterol concentration returned to normal. Doxepin has particularly potent H receptor antagonist properties, which suggests that blockade of Hi receptors may play a role in the cholesterol raising properties of some psychotropic drugs. 

Reboxetine is a selective noradrenaline re-uptake inhibitor with low affinity for a-adrenoceptors and muscarinic receptors. In controlled trials the following adverse events occurred significantly more often with reboxetine than with placebo dry mouth (27%), constipation (17%), increased sweating (14%), insomnia (14%), urinary... 

Side effects may appear anticholinergic , but reboxetine does not directly block muscarinic receptors... 

Reboxetine. Reboxetine (21) is a norepinephrine-selective reuptake inhibitor that lacks affinity for most of the monoamine receptors. It thus does not exhibit the typical side-effect profile of the tricyclics. Nevertheless, side effects include increased sweating, postural hypotension (leading to dizziness), dry mouth, constipation, blurred vision, impotence, and dysuria. Tachycardia and urinary retention have also been reported (59). There is no evidence of cardiotoxicity and sexual dysfunction seems to be rare. In contrast to some of the earlier tricyclics that are sedative, reboxetine is nonsedating and can cause insomnia (60,61).. 

Reboxetine is a potent inhibitor of noradrenaline reuptake. It has a weak effect on serotonin reuptake and no significant affinity for muscarinic receptors. 

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