Half a Century of Antidepressant Drugs

Fangmann, P; Assion, Hans‐Jörg; Juckel, Georg; González, Cecilio Álamo; López‐Muñoz, Francisco

doi:10.1097/jcp.0b013e3181627b60

Cited by 68 publications

(20 citation statements)

References 12 publications

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“…Both compounds enhance monoaminergic neurotransmitters (primarily serotonin and norepinephrine) function in the synapse and therefore acted as a springboard for the rational design of drugs which specifically enhance the transmission of these neuromodulators. Further, these findings resulted in the development of the monoamine hypothesis of depression [46, 47]. The monoamine hypothesis of depression postulates that the pathophysiological basis of depression is due to the deficient activity of monoamines in the central nervous system [48].…”

Section: Monoamine Theory Of Depressionmentioning

confidence: 99%

The Neural Plasticity Theory of Depression: Assessing the Roles of Adult Neurogenesis and PSA-NCAM within the Hippocampus

2013

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Depression is a devastating and prevalent disease, with profound effects on neural structure and function; however the etiology and neuropathology of depression remain poorly understood. Though antidepressant drugs exist, they are not ideal, as only a segment of patients are effectively treated, therapeutic onset is delayed, and the exact mechanism of these drugs remains to be elucidated. Several theories of depression do exist, including modulation of monoaminergic neurotransmission, alterations in neurotrophic factors, and the upregulation of adult hippocampal neurogenesis, and are briefly mentioned in the review. However none of these theories sufficiently explains the pathology and treatment of depression unto itself. Recently, neural plasticity theories of depression have postulated that multiple aspects of brain plasticity, beyond neurogenesis, may bridge the prevailing theories. The term “neural plasticity” encompasses an array of mechanisms, from the birth, survival, migration, and integration of new neurons to neurite outgrowth, synaptogenesis, and the modulation of mature synapses. This review critically assesses the role of adult hippocampal neurogenesis and the cell adhesion molecule, PSA-NCAM (which is known to be involved in many facets of neural plasticity), in depression and antidepressant treatment.

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Section: Monoamine Theory Of Depressionmentioning

confidence: 99%

The Neural Plasticity Theory of Depression: Assessing the Roles of Adult Neurogenesis and PSA-NCAM within the Hippocampus

2013

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“…Many of these novel compounds were molecularly modified from the classic antihistamine structure. One compound in particular, G22355 (imipramine), was derived from promethazine by substituting a sulfur bridge of the phenothiazine ring with an ethylene bridge (Domino, 1999; Fangmann, Assion, Juckel, Gonzalez, & Lopez-Munoz, 2008). The Geigy Chemical Corp supplied imipramine, which was synthesized by Hafliger and Schinder, to Dr. Roland Kuhn to test in psychiatric patients.…”

Section: Monoamine Hypothesis and Monoamine Based Pharmacological Trementioning

confidence: 99%

A brief history of the development of antidepressant drugs: From monoamines to glutamate.

Hillhouse

Porter

2015

Experimental and Clinical Psychopharmacology

474

243

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Major depressive disorder (MDD) is a chronic, recurring, and debilitating mental illness that is the most common mood disorder in the United States. It has been almost 50 years since the monoamine hypothesis of depression was articulated, and just over 50 years since the first pharmacological treatment for MDD was discovered. Several monoamine-based pharmacological drug classes have been developed and approved for the treatment of MDD; however, remission rates are low (often less than 60%) and there is a delayed onset before remission of depressive symptoms is achieved. As a result of a “proof-of-concept” study in 2000 with the noncompetitive NMDA antagonist ketamine, a number of studies have examined the glutamatergic systems as viable targets for the treatment of MDD. This review will provide a brief history on the development of clinically available antidepressant drugs, and then review the possible role of glutamatergic systems in the pathophysiology of MDD. Specifically, the glutamatergic review will focus on the N-methyl-D-aspartate (NMDA) receptor and the efficacy of drugs that target the NMDA receptor for the treatment of MDD. The noncompetitive NMDA receptor antagonist ketamine, which has consistently produced rapid and sustained antidepressant effects in MDD patients in a number of clinical studies, has shown the most promise as a novel glutamatergic-based treatment for MDD. However, compounds that target other glutamatergic mechanisms, such as GLYX-13 (a glycine-site partial agonist at NMDA receptors) appear promising in early clinical trials. Thus, the clinical findings to date are encouraging and support the continued search for and the development of novel compounds that target glutamatergic mechanisms.

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“…The compound, now known as imipramine, was presented by Kuhn in 1957 as the first representative of the tricyclic antidepressants (TCAs) (Brown and Rosdolsky, 2015). In the period between 1960 and 1979, many different TCAs were developed, including amitriptyline, nortriptyline, desipramine, trimipramine, protryptyline, iprindol, dothiepin and clomipramine (Fangmann et al, 2008; López-Muñoz and Alamo, 2009). First tricyclic antidepressants were shown to inhibit the uptake of NA.…”

Section: From the Drugs To Monoaminesmentioning

confidence: 99%

Monoaminergic and Histaminergic Strategies and Treatments in Brain Diseases

et al. 2016

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The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems. Later, some dramatic side effects associated with older medicines were shown to disappear with new chemical compounds targeting the origin of the therapeutic benefit more specifically. The increased knowledge regarding the function and interaction of the monoaminergic systems in the brain resulting from in vivo neurochemical and neurophysiological studies indicated new monoaminergic targets that could achieve the efficacy of the older medicines with fewer side-effects. Yet, this accumulated knowledge regarding monoamines did not produce valuable strategies for diseases where no monoaminergic drug has been shown to be effective. Here, we emphasize the new therapeutic and monoaminergic-based strategies for the treatment of psychiatric diseases. We will consider three main groups of diseases, based on the evidence of monoamines involvement (schizophrenia, depression, obesity), the identification of monoamines in the diseases processes (Parkinson's disease, addiction) and the prospect of the involvement of monoaminergic mechanisms (epilepsy, Alzheimer's disease, stroke). In most cases, the clinically available monoaminergic drugs induce widespread modifications of amine tone or excitability through neurobiological networks and exemplify the overlap between therapeutic approaches to psychiatric and neurological conditions. More recent developments that have resulted in improved drug specificity and responses will be discussed in this review.

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Half a Century of Antidepressant Drugs

Cited by 68 publications

References 12 publications

The Neural Plasticity Theory of Depression: Assessing the Roles of Adult Neurogenesis and PSA-NCAM within the Hippocampus

The Neural Plasticity Theory of Depression: Assessing the Roles of Adult Neurogenesis and PSA-NCAM within the Hippocampus

A brief history of the development of antidepressant drugs: From monoamines to glutamate.

Monoaminergic and Histaminergic Strategies and Treatments in Brain Diseases

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