Selective norepinephrine reuptake inhibitors (sNRIs) are a class of drugs that have been marketed as antidepressants and are used for various mental disorders, mainly depression and attention-deficit hyperactivity disorder (ADHD). The norepinephrine transporter (NET) serves as the fundamental mechanism for the inactivation of noradrenergic signaling because of the NET termination in the reuptake of norepinephrine (NE). The selectivity and mechanism of action for the NRI drugs remain mostly unresolved and, to date, only a limited number of NRI-selective inhibitors are available. The first commercially available selective NRI was the drug reboxetine (Edronax), developed as a first-line therapy for major depressive disorder. Atomoxetine (Strattera) is another potent and selective NRI which is also effective and well tolerated for the treatment of ADHD in adults; it may also be a new treatment option for adults with ADHD, particularly for those patients at risk of substance abuse.
Medical uses
Atomoxetine is sold under the brand name Strattera and was first approved for medical use in the United States in 2002. Its indication is for the treatment of attention deficit hyperactivity disorder (ADHD) in kids over 6 years of age, adolescents and adults. Atomoxetine selectively inhibits norepinephrine reuptake by blocking the presynaptic norepinephrine transporter (NET) in the brain. Research has suggested that it also inhibits the reuptake of serotonin by binding to the selective serotonin transporter. However it is not known whether the therapeutic effects of atomoxetine is due to its blockage of the NET or both norepinephrine- and serotonin transporters. Reboxetine is the active ingredient, sold under the brand name Edronax. Reboxetine is a selective norepinephrine reuptake inhibitor and acts by binding to the NET and block the reuptake of norepinephrine in the extracellular fluids. Its indication is for acute treatment of depression or major depression disorder. Reboxetine was first approved for marketing in Europe in 1997, however, in the United States its application for approval was rejected.
Adverse effects
Side effects
Selective NRIs are generally well tolerated but the most common side effects reported are headache, dry mouth, abdominal pain, loss of appetite, nausea, vomiting and drowsiness. An increase in heart rate and blood pressure have been reported but are usually not clinically important. Sexual adverse effects are mostly related to male arousal difficulties and decreased libido in both men and women, but they are significantly less common than with serotonergic drugs. Other side effects are urinary retention, constipation, sweating and insomnia. What can be considered serious side effects are thoughts of suicide, aggressiveness and hallucinations.
Interactions
If people are using sNRI drugs they should not take MAO inhibitors at the same time. That can increase the plasma concentration of NRIs in the body.
Beware of taking atomoxetine in combination with: CYP2D6 inhibitors (e.g., fluoxetine, paroxetine and quinidine) can increase exposure for atomoxetine and it can also increase atomoxetine steady-state plasma concentration. Antihypertensive drugs because it can possibly increase the blood pressure β2-agonist e.g. albuterol because it may increase the efficacy of albuterol on the cardiovascular system. Medicines that affect norepinephrine (e.g. venlafaxine, imipramine, mirtazapine) should be used with caution when administered with atomoxetine due to possible synergy or synergistic effects on pharmacodynamic effects.
Beware of taking reboxetine in combination with: Antifungals, e.g. ketoconazole. Antibiotics, e.g. erythromycin, rifampicin. Ergot derivatives used to treat migraine or Parkinson's disease may cause an increase in blood pressure. Any potassium-depleting diuretics (medicines for eliminating water), e.g. thiazides. Carbamazepine and phenobarbital, medicines used to control fits or seizures. Herbal medicines that contains St. John's Wort.