are treated with an initial dose of reboxetine 8 mg/day, most often as a divided dose. depending upon patient tolerance and need, the dose can be increased up to 10 mg/day. doses over 12 mg/day are not recommended. doses should be adjusted in renal failure, hepatic insufficiency and in geriatric patients. structure and function structure activity relationship aryloxy propylamine moiety of atomoxetine and reboxetine atomoxetine contains an aryloxy propylamine moiety that has been linked to monoamine reuptake inhibitory activity. it's selectivity to the norepinephrine transporter (net) is due to its methyl substituent in the 2’ position on the phenyl ring. research has shown that a methyl group in position 2’ provides more affinity towards net than a methoxy group in the same position. the amine group of atomoxetine binds to the amino acids of net with a salt bridge and hydrogen bonds while the phenyl and methylphenyl groups have hydrophobic interactions. reboxetine has two chiral centers and the active ingredient is a mixture of the (r,r)-(-)- and (s,s)-(+) enantiomers. reboxetine, like atomoxetine, contains an aryloxy propylamine moiety and has an ethoxy group in position 2’ on the phenyl ring. but the main difference from atomoxetine is the morpholine group instead of a secondary amine. the morpholine group of reboxetine forms a salt bridge and hydrogen bonds with the amino acids of net. while the phenyl and ethyloxyphenyl groups form hydrophobic interactions. the aryloxy propylamine moiety is also found in many other monoamine reuptake inhibitors, but the placement of substituents on the phenyl ring determine the selectivity. compounds with substituents in position 2’ have selectivity for net. compounds with substituents in position 4’ are selective serotonin reuptake inhibitors e.g. fluoxetine and paroxetine. then there is duloxetine which has a phenyl group attached at positions 2’ and 3’ and has a similar affinity for both transporters. history in the 1950s, major breakthrough in psychopharmacology occurred around the world. then throughout the 1960s and 1970s major advances were made in synthesizing and identifying psychoactive drugs which were useful in the treatment of various mental disorders. here, scientists had realised that these drugs interact with receptors located on neurons that led to changes in neural functioning. the connection was made shortly after the discovery of catecholamines having effects on emotion, relating to depression, and was of wide interest. discovery was made on the decreased levels of certain neurotransmitters, catecholamines such as norepinephrine, dopamine and serotonin, and their role in the pathogenesis of depression. these past discoveries in psychopharmacology led to the development of antidepressants and a range of drugs with different functions on those neurotransmitters. but a new generation of antidepressants were resulted from the discovery of ssris, e.g. fluoxetine. although ssris are a group of effective antidepressant drugs with considerable few severe side effects, they are not universally effective and can also have a few unpleasant side effects, such as weight gain, sleep disturbances and anxiety. pharmacologically and chemically unrelated to ssris, the past four decades, norepinephrine has been asserted to play an important, possibly primary, role in the treatment of mental disorders. this was from the notion that depression was primarily due to norepinephrine deficits, partly based on the fact that drugs that relieve depression increase brain norepinephrine levels. to date, a great number of potent and selective (also mixed) net inhibitors, e.g. selective nris, have been marketed as antidepressants. the first commercially available selective norepinephrine reuptake inhibitor (nri) was reboxetine (edronax) and was developed as a first line therapy for major depressive disorder. the selectivity of reboxetine for the net results in benign side effect profile because the drug is well tolerated. in the laboratories of chemistry of farmitalia carlo erba (milan, italy), reboxetine was synthesized according to the general method described by melloni et al. in 1993 kabi pharmacia, swedish based pharmaceutical giant, bought farmitalian and in 2003 pfizer bought pharmacia. atomoxetine (strattera) is another potent and selective nri which is also effective and well tolerated treatment for adults with adhd. this drug was the first adhd treatment to be specially approved for adult use. studies showed that atomoxetine is a nonstimulant and carries negligible risk of abuse. this discovery was groundbreaking as a beneficial new treatment option for adults with adhd, specially those patients at risk of substance abuse.