EurekaMag.com logo
+ Site Statistics
References:
53,623,987
Abstracts:
29,492,080
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Trends in the development of new antidepressants. Is there a light at the end of the tunnel?



Trends in the development of new antidepressants. Is there a light at the end of the tunnel?



Current Medicinal Chemistry 11(7): 925-943



Since the introduction of tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) in mid-1950's, treatment of depression has been dominated by monoamine hypotheses. The well-established clinical efficacy of TCAs and MAOIs is due, at least in part, to the enhancement of noradrenergic or serotonergic mechanisms, or to both. Unfortunately, their very broad mechanisms of action also include many unwanted effects related to their potent activity on cholinergic, adrenergic and histaminergic receptors. The introduction of selective serotonin reuptake inhibitors (SSRIs) over twenty years ago had been the next major step in the evolution of antidepressants to develop drugs as effective as the TCAs but of higher safety and tolerability profile. During the past two decades SSRIs (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram) gained incredible popularity and have become the most widely prescribed medication in the psychiatric practice. The evolution of antidepressants continued resulting in introduction of selective and reversible monoamine oxidase inhibitors (eg. moclobemid), selective noradrenaline (eg. reboxetine), dual noradrenaline and serotonin reuptake inhibitors (milnacipram, venlafaxin, duloxetin) and drugs with distinct neurochemical profiles such as mirtazapine, nefazadone and tianeptine. Different novel serotonin receptor ligands have also been intensively investigated. In spite of the remarkable structural diversity, most currently introduced antidepressants are 'monoamine based'. Furthermore, these newer agents are neither more efficacious nor rapid acting than their predecessors and approximately 30% of the population do not respond to current therapies. By the turn of the new millennium, we are all witnessing a result of innovative developmental strategies based on the better understanding of pathophysiology of depressive disorder. Several truly novel concepts have emerged suggesting that the modulation of neuropeptide (substance P, corticotrophin-releasing factor, neuropeptide Y, vasopressin V1b, melanin-concentrating hormone-1), N-methyl-D-aspartate, nicotinic acetylcholine, dopaminergic, glucocorticoid, delta-opioid, cannabinoid and cytokine receptors, gamma-amino butyric acid (GABA) and intracellular messenger systems, transcription, neuroprotective and neurogenic factors, may provide an entirely new set of potential therapeutic targets, giving hope that further major advances might be anticipated in the treatment of depressive disorder soon. The goal of this review is to give a brief overview of the major advances from monoamine-based treatment strategies, and particularly focus on the new emerging approaches in the treatment of depression.

(PDF same-day service: $19.90)

Accession: 035985579

Download citation: RISBibTeXText

PMID: 15078174

DOI: 10.2174/0929867043455594



Related references

Studying new antidepressants: if there were a light at the end of the tunnel, could we see it?. Journal of Clinical Psychiatry 63 Suppl 2: 24-28, 2004

Cigarette smoking and lung cancer trends. A light at the end of the tunnel?. Chest 111(5): 1414-1416, 1997

Current trends in the development of new antidepressants. Current Medicinal Chemistry 8(2): 89-100, 2001

Antidepressants, catecholamines and 5-hydroxyindoles. Trends towards a more specific research in the field of antidepressants. Psychiatria, Neurologia, Neurochirurgia 70(3): 219-233, 1967

Development trends in tunnel boring machines for hard rock application. Pages 388-394:, 1978

Light at the end of the tunnel of antibiotic development. Lancet. Infectious Diseases 13(12): 1008-1009, 2014

Barlow's Repair: Light in the Dark Tunnel: A Case Report Could Omit 'Light in A Dark Tunnel'. Medical Journal of Malaysia 70(2): 106-107, 2015

Discovery and development of 5-HT(₂C) receptor agonists for obesity: is there light at the end of the tunnel?. Future Medicinal Chemistry 2(12): 1761-1775, 2011

Light intensity distribution optimization for tunnel lamps in different zones of a long tunnel. Optics Express 22(19): 22952-22961, 2015

Is there Light at the End of the Tunnel? Controversies in the Diagnosis and Management of Carpal Tunnel Syndrome. Hand 5(4): 354-360, 2011

On-road emission factors from light-duty vehicles measured in Hsuehshan Tunnel (12.9 km), the longest tunnel in Asia. Environmental Monitoring and Assessment 153(1-4): 187-200, 2008

Symposium 6 second generations antidepressants and antidepressants in development chairman: m. Sandler (u.k.). Journal of Psychopharmacology 2(3-4): 179-182, 1988

Tunnel propagation after defibrillation: a light at the end of the tunnel. Heart Rhythm 7(7): 962-963, 2010

Studies on action spectra of light on gonadal development of the medaka, Oryzias latipes. 2. Effects of ultraviolet light, visible light, and critical wave length light on ovarian development. Journal of Hokkaido University of Education Section II B 33(1): 7-10, 1982

Tendon healing in a bone tunnel differs at the tunnel entrance versus the tunnel exit: an effect of graft-tunnel motion?. American Journal of Sports Medicine 34(11): 1790-1800, 2006