Book contents
- Frontmatter
- Contents
- List of contributors
- Acknowledgements
- Introduction: revision of an old transmitter
- Part I The neurobiology of norepinephrine
- Part II Norepinephrine and behavior
- Part III The biology of norepinephrine in CNS pathology
- Part IV Psychopharmacology of norepinephrine
- 17 Actions of antidepressant and other drugs on norepinephrine systems
- 18 The clinical role of norepinephrine antidepressants in depression and anxiety disorders
- 19 Norepinephrine in attention-deficit/hyperactivity disorder
- 20 Psychopharmacology of norepinephrine in eating disorders
- 21 Role of norepinephrine in substance abuse
- Index
18 - The clinical role of norepinephrine antidepressants in depression and anxiety disorders
from Part IV - Psychopharmacology of norepinephrine
Published online by Cambridge University Press: 07 September 2009
- Frontmatter
- Contents
- List of contributors
- Acknowledgements
- Introduction: revision of an old transmitter
- Part I The neurobiology of norepinephrine
- Part II Norepinephrine and behavior
- Part III The biology of norepinephrine in CNS pathology
- Part IV Psychopharmacology of norepinephrine
- 17 Actions of antidepressant and other drugs on norepinephrine systems
- 18 The clinical role of norepinephrine antidepressants in depression and anxiety disorders
- 19 Norepinephrine in attention-deficit/hyperactivity disorder
- 20 Psychopharmacology of norepinephrine in eating disorders
- 21 Role of norepinephrine in substance abuse
- Index
Summary
Introduction
Since Roland Kuhn's observation of the antidepressant action of imipramine in 1958, noradrenergic antidepressants have played an important role in the treatment of depression. Because imipramine has a central place in the discovery of treatments for depression and anxiety, understanding its pharmacology is crucial. Although imipramine itself has affinity for the serotonin (5-HT) transporter, its metabolites, desipramine and hydroxy-desipramine, have greater affinity for the norepinephrine (NE) transporter. During chronic oral administration of imipramine in humans, median desipramine levels are about twice those of the parent compound, and hydroxy-desipramine, a NE reuptake inhibitor similar in potency to desipramine, is present at levels about 40% of those of desipramine. The net effect is that, during chronic administration of imipramine, about three-quarters of the total concentration of the drug is present as metabolites that act primarily on the noradrenergic system.
Imipramine also played an important role in the development of pharmacologic treatments of anxiety. Klein observed that patients with episodes of intense anxiety received benefit from imipramine that was not seen with phenothiazines or sedatives. He distinguished this syndrome, which later became known as “panic disorder,” from persistent anticipatory anxiety. Two decades later, Hoehn-Saric et al. demonstrated that imipramine was in fact effective in generalized anxiety as well, even if the response was not as dramatic as in panic disorder. These studies suggested the potential value of antidepressants for treatment of anxiety disorders. Ironically, imipramine was never approved for use in these anxiety syndromes.
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- Brain NorepinephrineNeurobiology and Therapeutics, pp. 535 - 556Publisher: Cambridge University PressPrint publication year: 2007
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