Fluoxetine: a case history of its discovery and preclinical development

Pérez-Caballero, Laura; Torres-Sánchez, Sonia; Bravo, Lidia; Micó, J.A.; Berrocoso, Esther

doi:10.1517/17460441.2014.907790

Cited by 128 publications

(99 citation statements)

References 87 publications

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“…Beyond their utility for the current studies, development of this experimental infrastructure fulfills an unmet need for the field, and will enable future mechanistic studies in octopuses. Moreover, this work demonstrates that medications currently in use or under investigation in humans (22,(28)(29)(30), Fig. 1.…”

mentioning

confidence: 57%

SLC6A4 binding site and acute prosocial effects of (+/-)-3,4-methylendioxymethamphetamine (MDMA) are evolutionarily conserved in Octopus bimaculoides

Edsinger¹,

Dölen

2018

Preprint

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ABSTRACT:Human and octopus lineages are separated by over 500 million years of evolution, and show divergent anatomical patterns of brain organization. Moreover, while humans exhibit highly complex social behaviors, octopuses are thought to be largely asocial and solitary. Despite these differences, growing evidence suggests that ancient neurotransmitter systems are shared across vertebrate and invertebrate species, and in many cases enable overlapping functions. Here we provide evidence that, as in humans, the atypical amphetamine derivative (+/-)-3,4-methylendioxymethamphetamine (MDMA) enhances acute prosocial behaviors in Octopus bimaculoides. This finding is paralleled by the evolutionary conservation of the serotonin transporter (SERT, encoded by the Slc6A4 gene) binding site of MDMA in the O. bimaculoides genome. Taken together, these data provide evidence that the neural mechanisms subserving social behaviors exist in O. bimaculoides, and indicate that the role of serotonergic neurotransmission in regulating social behaviors is evolutionarily conserved.ONE SENTENCE SUMMARY:Here we provide evidence that the atypical amphetamine derivative (+/-)-3,4-methylendioxymethamphetamine (MDMA) increases acute social approach behaviors in Octopus bimaculoides, a finding that is paralleled by the evolutionary conservation of the SLC6A4 binding site of MDMA.

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mentioning

confidence: 57%

SLC6A4 binding site and acute prosocial effects of (+/-)-3,4-methylendioxymethamphetamine (MDMA) are evolutionarily conserved in Octopus bimaculoides

Edsinger¹,

Dölen

2018

Preprint

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“…Its unique properties and appropriate clinical efficacy established the SERT as an important target in the treatment of depression (Perez-Caballero et al, 2014). Fluoxetine is, in fact, not highly selective toward the SERT whereas citalopram, escitalopram, fluvoxamine, paroxetine or sertraline block the SERT more selectively (Thomas et al, 1987; Jacquot et al, 2007).…”

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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“…Of those, tens of molecules are tested in preclinical animal models of the disease. In addition to toxicity, molecules are tested for their pharmacokinetics (PK), bioavailability at the target organ, in vivo target engagement, biological or chemical response that can be directly linked to the molecular action in the organism (pharmacodynamics, PD), and efficacy in the animal model [12,13]. This process builds confidence that the handful of molecules with the best in vitro and in vivo profiles will also be safe, engage the intended target, and potentially treat the disease in humans.…”

Section: Introduction and Scopementioning

confidence: 99%

The role of fMRI in drug development

Carmichael

Schwarz

Chatham

et al. 2018

Drug Discovery Today

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Functional magnetic resonance imaging (fMRI) has been known for over a decade to have the potential to greatly enhance the process of developing novel therapeutic drugs for prevalent health conditions. However, the use of fMRI in drug development continues to be relatively limited because of a variety of technical, biological, and strategic barriers that continue to limit progress. Here, we briefly review the roles that fMRI can have in the drug development process and the requirements it must meet to be useful in this setting. We then provide an update on our current understanding of the strengths and limitations of fMRI as a tool for drug developers and recommend activities to enhance its utility.

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Fluoxetine: a case history of its discovery and preclinical development

Cited by 128 publications

References 87 publications

SLC6A4 binding site and acute prosocial effects of (+/-)-3,4-methylendioxymethamphetamine (MDMA) are evolutionarily conserved in Octopus bimaculoides

SLC6A4 binding site and acute prosocial effects of (+/-)-3,4-methylendioxymethamphetamine (MDMA) are evolutionarily conserved in Octopus bimaculoides

Monoaminergic and Histaminergic Strategies and Treatments in Brain Diseases

The role of fMRI in drug development

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