Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application

Pharmacology & Therapeutics
Mark J Millan

Abstract

Major depression is a debilitating and recurrent disorder with a substantial lifetime risk and a high social cost. Depressed patients generally display co-morbid symptoms, and depression frequently accompanies other serious disorders. Currently available drugs display limited efficacy and a pronounced delay to onset of action, and all provoke distressing side effects. Cloning of the human genome has fuelled expectations that symptomatic treatment may soon become more rapid and effective, and that depressive states may ultimately be "prevented" or "cured". In pursuing these objectives, in particular for genome-derived, non-monoaminergic targets, "specificity" of drug actions is often emphasized. That is, priority is afforded to agents that interact exclusively with a single site hypothesized as critically involved in the pathogenesis and/or control of depression. Certain highly selective drugs may prove effective, and they remain indispensable in the experimental (and clinical) evaluation of the significance of novel mechanisms. However, by analogy to other multifactorial disorders, "multi-target" agents may be better adapted to the improved treatment of depressive states. Support for this contention is garnered from a broad pal...Continue Reading

References

Apr 2, 1979·Clinica Chimica Acta; International Journal of Clinical Chemistry·M SandlerA Coppen
Jan 1, 1976·Annual Review of Microbiology·R A Jensen
Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J Brosius, S J Gould
Apr 17, 1992·Journal of Medicinal Chemistry·S YousB Guardiola-Lemaitre
Mar 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·R SpanagelT S Shippenberg
Feb 1, 1992·Pharmacology, Biochemistry, and Behavior·B Guardiola-LemaîtreR D Porsolt
Jan 1, 1992·Pharmacology & Therapeutics·J A Pratt
Jan 1, 1992·Brain Research. Molecular Brain Research·E D WeinerH M Lachman
Aug 1, 1992·Archives of General Psychiatry·R M BencaJ C Gillin
Jun 24, 1992·European Journal of Pharmacology·C Durlach-Misteli, J M Van Ree
Aug 15, 1992·Biological Psychiatry·J M De la Fuente, J Mendlewicz
Oct 1, 1992·Naunyn-Schmiedeberg's Archives of Pharmacology·E P FintaP Illes
Nov 1, 1992·Journal of Affective Disorders·K DaimonS Takahashi
May 8, 1992·The Journal of Comparative Neurology·J C BittencourtP E Sawchenko
May 1, 1992·Pharmacology, Biochemistry, and Behavior·G PerraultD J Sanger
Jul 1, 1992·Pharmacopsychiatry·L LauritzenP Bech
Jan 14, 1992·European Journal of Pharmacology·A Fernández-GuastiK Larsson
Jun 1, 1992·The American Journal of Psychiatry·A F Schatzberg, A J Rothschild
Jan 1, 1992·Journal of Neural Transmission. General Section·J HyttelC Sánchez
Jan 1, 1991·Progress in Neuro-psychopharmacology & Biological Psychiatry·A A Boulton
Dec 1, 1991·Biological Psychiatry·R S Kahn, S Wetzler
Jan 1, 1991·Progress in Brain Research·G Aston-JonesB Astier
Jan 1, 1990·Neuropharmacology·C M FattacciniM Hamon
Jul 1, 1991·Pharmacology, Biochemistry, and Behavior·N V Watson, B B Gorzalka
Oct 1, 1991·Journal of Geriatric Psychiatry and Neurology·C P Pollak, D Perlick
Dec 1, 1991·International Clinical Psychopharmacology·J F Deakin

❮ Previous
Next ❯

Citations

Oct 11, 2012·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Agnieszka ZagórskaGabriel Nowak
Jul 27, 2007·Psychopharmacology·Donald F SmithRaben Rosenberg
Aug 7, 2010·Psychopharmacology·Winand H DittrichNaomi A Fineberg
Nov 26, 2010·Psychopharmacology·Gregory V Carr, Irwin Lucki
Dec 27, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Mark J Millan
Oct 6, 2011·Journal of the American Chemical Society·Jerry C ChangSandra J Rosenthal
Sep 4, 2012·Journal of Medicinal Chemistry·Younghue HanHoh-Gyu Hahn
Aug 8, 2013·Journal of Medicinal Chemistry·Jens-Uwe Peters
Oct 22, 2008·Nature Chemical Biology·Andrew L Hopkins
Oct 17, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Zaorui ZhaoJames M O'Donnell
Apr 18, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Mei HuangHerbert Y Meltzer
Apr 18, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Zaorui ZhaoJames M O'Donnell
Jun 26, 2010·Nature Reviews. Drug Discovery·Christian de BodinatMark J Millan
Apr 27, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jeanne StemmelinGuy Griebel
Oct 25, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Karl EbnerNicolas Singewald
Dec 14, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jonathan P GodboutRodney W Johnson
Aug 19, 2007·The Pharmacogenomics Journal·Sami AnttilaTerho Lehtimäki
May 27, 2010·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Fereydoun HormozdiariS Cenk Sahinalp
Dec 30, 2009·Briefings in Bioinformatics·Jing ZhaoWeidong Zhang
Apr 22, 2008·Addiction Biology·Fabrício A Moreira, Beat Lutz
Feb 6, 2008·PLoS Computational Biology·Peter Dayan, Quentin J M Huys
Jan 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Erwan Le MaîtreTomas G M Hökfelt
Dec 7, 2013·Psychopharmacology·Bibiana Mozzaquatro GaiCristina Wayne Nogueira
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Gabriella JuhaszGyorgy Bagdy
Apr 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·B ChanrionP Marin

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiovascular Disease Pathophysiology

Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.

Alzheimer's Disease: Genetics

Alzheimer's disease is a neurodegenerative disease. Discover genetic and epigenetic aspects of Alzheimer’s disease, including genetic markers and genomic structural variations with this feed.

Astrocytes in Repair & Regeneration

Astrocytes are glial cells found within the CNS and are able to regenerate new neurons. They become activated during CNS injury and disease. The activation leads to the transcription of new genes and the repair and regeneration of neurons. Discover the latest research on astrocytes in repair and regeneration here.

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Alzheimer's Disease: Transcription

Impaired transcription is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD). Here are the latest discoveries pertaining to transcription and AD.

Barrett Esophagus

Barrett’s esophagus if a serious complication of gastroesophageal reflux disease during which the normal esophageal lining changes to tissue that resembles intestinal lining. Here is the latest research.

Basal Forebrain- Circuits

Basal forebrain is a region in the brain important for production of acetylcholine and is the major cholinergic output of the CNS. Discover the latest research on circuits in the basal forebrain here.

Autoimmune Polyendocrinopathies

Autoimmune polyendocrinopathies, also called polyglandular autoimmune syndromes (PGASs), or polyendocrine autoimmune syndromes(PASs), are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected. Discover the latest research on autoimmune polyendocrinopathies here.

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Antipsychotic Drugs

Antipsychotic drugs are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. Discover the latest research on antipsychotic drugs here

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Autoimmune Polyendocrine Syndromes

This feed focuses on a rare genetic condition called Autoimmune Polyendocrine Syndromes, which are characterized by autoantibodies against multiple endocrine organs. This can lead to Type I Diabetes.

Barrel cortex

Here is the latest research on barrel cortex, a region of somatosensory and motor corticies in the brain, which are used by animals that rely on whiskers for world exploration.

Astrocytes in Parkinson Disease

Parkinson's disease (PD) is a neurodegenerative disorder caused by the progressive loss of dopaminergic neurons. Some PD-genes may be associated with astrocyte dysfunction. Discover the latest research on astrocytes in Parkinson's disease here.

Amygdala: Sensory Processes

Amygdalae, nuclei clusters located in the temporal lobe of the brain, play a role in memory, emotional responses, and decision-making. Here is the latest research on sensory processes in the amygdala.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Alzheimer's Disease: Neuroimaging

Neuroimaging can help identify pathological hallmarks of Alzheimer's disease (AD). Here is the latest research on neuroimaging modalities, including magnetic resonance imaging and positron emission tomography, in AD.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Basal ganglia in Parkinson's disease (MDS)

The basal ganglia is comprised of the neostriatum, the external and internal pallidal segments, the subthalamic nucleus, the substantia nigra pars reticulata, and the pars compacta of the substantia nigra. The basal ganglia circuitry is responsible for the correct execution of voluntary movements and is implicated in Parkinson's disease. Here is the latest research investigating the basal ganglia in Parkinson's disease.

Autoimmune Thyroiditis

Autoimmune thyroiditis is an inflammatory disease of thyroid gland due to autoimmune responses leading to lymphocytic infiltration of the gland. It is characterized by the presence of circulating thyroid antigen-specific T-cells and thyroid autoantibodies. Discover the latest research on autoimmune thyroiditis here.