Reboxetin

Noradrenaline transporters (NAT) are localized in the presynaptic plasma membrane of adrenergic nerve terminals. They belong to a family of proteins with 12 putative transmembrane proteins which are responsible for recycling of released neurotransmitters (noradrena-line/adrenaline, dopamine, serotonin, amino acid transmitters) back into the presynaptic nerve ending. Noradrenaline transporters can be blocked by a number of different antidepressant drags, including tricyclic antidepressants (e.g. desipramine) and selective noradrenaline reuptake inhibitors (e.g. reboxetine). 

Selective noradrenaline reuptake inhibitors (SNRIs) are a group of drugs, which act as antidepressants by the selective inhibition of the reuptake of noradrenaline from the synaptic cleft via the selective blockade of the noradrenaline-specific neurontransmitter transporter (e.g. reboxetine). 

CijHkjO 104-54-1) see Chloramphenicol Zipeprol rrans-cinnamyl alcohol (C HiqO 4407-36-7) see Reboxetine cinnamyl bromide... 

Butacaine Butethuinine Leucinocaine Methotrexate Procainamide Procaine Reboxetine 2>nitrobenzoyl chloride... 

NART Inhibition of noradrenaline reuptake Maprotiline Viloxazine Reboxetine Hp and oti-antagonism... 

Dostert, P, Benedetti, MS and Poggesi, I (1997) Review of the pharmacokinetics and metabolism of reboxetine, a selective noradrenaline reuptake inhibitor. Eur. Neuropsychopharmacol. 1 (Suppl. 1) S23-S35. 

Massana, J. (1998). Reboxetine versus fluoxetine an overview of efficacy and tolerability. J. Clin. 

Scates, A. C. Doraiswamy, P. M. (2000). Reboxetine a selective norepinephrine reuptake inhibitor for the treatment of depression. Ann. Pharmacother., 34, 1302-12. 

Shen, Y. F., Li, H. F., Ma, C. et al. (2005). Comparison of reboxetine with fluoxetine in treatment of depressions randomized double-blind multicenter study. Chinese Journal of New Drugs and Clinical Remedies, 24(8), 619-23. 

The combination of antidepressants is a common clinical practice. The most usual pharmacological profile is serotoninergic-noradrenergic (96%) and the most popular combinations are selective 5-HT reuptake inhibitor (SSRI) + mir-tazapine, SSRI + reboxetine, and SSRI + TCAs (De la Gandara et al. 2005). 

Reboxetine NP Silica, Cyanopropyl Chiracel OD-H Walters and Buist, 1998... 

Walters, R.R., Buist, S.C. (1998). Improved enantioselective method for the determination of the enantiomers of reboxetine in plasma by solid-phase extraction, chiral derivitization, and column-switching high-performance liquid chromatography with fluorescence detection. J. Chromatogr. A 828, 167-176. 

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. 

These types of antidepressant were introduced around 10 years after the SSRIs. They include the serotonin noradrenaline reuptake inhibitor venlafaxine and the selective noradrenaline reuptake inhibitor reboxetine. Although there are fewer data about these drugs, clinical experience has shown they are well tolerated and, unlike the SSRIs, they are only weak inhibitors of drug metabolism (Kent, 2000). Depression is a common psychiatric disorder seen in the elderly and often remains untreated or inadequately treated (Forsell and Fastbom, 2000). Venlafaxine was shown to improve the mood in a group of 36 older patients without any effect on cognitive function, an important consideration where there is the possibility of the coexistence of mild or undiagnosed dementia (Tsolaki et al., 2000). 

Reboxetine An antidepressant that is a selective noradrenaline reuptake inhibitor. 

Versiani M, Mehilane L, Gaszner P, Arnaud-Castiglioni R. Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder. J Clin Psychiatry 1999 60 400-406. 

Although there is structural homology among the transporters for 5-HT, norepinephrine and dopamine, some drugs exhibit great selectivity at inhibiting the activity of just one of these proteins. For example, the selective norepinephrine re-uptake inhibitor reboxetine is 150 times more potent at inhibiting norepinephrine transport... 

Compound 10, representing a series of NRIs structurally similar to reboxetine, has been reported to be a potent and selective inhibitor of NET (K-, — 3.2 nM) [24], In an a-methyl-m-tyrosine (a-MMT)-induced cortical NE depletion model in rats, 10 showed dose-dependent activity after oral administration with a measured ED50 of 18mg/kg. WAY-256805 (11), an NRI, was recently reported to be efficacious in the mouse tail suspension model [25]. 

Wienkers, L.C., Allievi, C., Hauer, M.J. and Wynalda, M.A. (1999) Cytochrome P-450-mediated metabolism of the individual enantiomers of the antidepressant agent reboxetine in human liver microsomes. Drug Metabolism and Disposition, 27 (11), 1334-1340. 

Atypical antidepressants Bupropion Duloxetine Mianserin Mirtazapine Nefazodone Reboxetine Trazodone Venlafaxine... 

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