Validation of experimental medicine methods in psychiatry: The P1vital approach and experience

Dawson, Gerard R.; Craig, Katy; Dourish, C T

doi:10.1016/j.bcp.2011.03.013

Cited by 14 publications

(12 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Published evidence for behavioural specificity is missing also for lorcaserin [348], although this is also true for many other compounds still undergoing clinical testing [298]. In this context it may be worth considering that translational medicine of disease/obesity between phase 1 and phase 2 of clinical trials could provide early inside in efficacy and safety in humans [349]. Such a translational approach using the 5-HT2C/1B agonist mCPP has recently been exemplified in humans [350].…”

Section: Serotonin and The Pharmacotherapy Of Obesitymentioning

confidence: 99%

Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

270

167

View full text Add to dashboard Cite

Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and 'true' 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 IntroductionWhat are the behavioural and physiological mechanisms that promote satiety? How is satiety defined? Satiety can be seen as a behavioural state which arises from food consumption and suppresses the initiation of eating for a particular period of time [1]. This description alone suggests a high degree of complexity as peripheral post-ingestive and post-absorptive signals need to be relayed to the brain where they are integrated with other signals to produce (or not) the behavioural state called satiety. The state of satiety is brought about a process called satiation, where sensory, cognitive and early post-ingestive mechanisms bring feeding to a halt and thus stopping a meal. Promoting satiation alone must not necessarily lead to reduced total food intake as the frequency of meals could be increased subsequently. Many peripheral and brain mechanisms have been identified that are involved in the expression satiety and it has been suggested that serotonin accelerates satiation and prolongs satiety [2]. In the following, we will review the role of serotonin in satiety in more detail 1 . The reader will see that, despite immense progress made during the last years, the field is still far from being resolved.As serotonin (5-Hydroxytryptamine; 5-HT) is a phylogenetically old neurotransmitter, various functions had time to evolve in different phyla, but maybe also in different species. 5-HT receptors exist in animal cells for millions of years and they are as old as adrenoreceptors ore some peptide receptors, possibly even older [5,6]. Even in invertebrates such as molluscs (Aplysia californica) and annelids (Hirudo medicinalis), 5-HT might functionally be related to food intake [7]. 5-HT is involved in feeding even in the honeybee where it has separate effects in the gut and in the insect brain [8]. In general, however, 5-HT seems rather to be involved in appetitive behaviours in invertebrates whereas it has more of a satiating effect in vertebrates [9]. In general, 5-HT neurons seem to be more extensively distributed throughout the body in lower animals than in higher animals including mammals where 5-HT neurones...

show abstract

Section: Serotonin and The Pharmacotherapy Of Obesitymentioning

confidence: 99%

Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

270

167

View full text Add to dashboard Cite

show abstract

“…It is increasingly recognised by the pharmaceutical industry that the introduction of Experimental (Translational) Medicine models at the interface between Phase 1 and Phase 2 clinical trials provides a more effective approach to assessing drug efficacy and safety before large scale trials are undertaken (Dawson et al 2011). Initial efficacy testing of novel compounds can also be conducted in healthy volunteers to assess safety issues that might pose risks for vulnerable patient populations (Dourish et al 2008).…”

mentioning

confidence: 99%

Effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine on appetite, food intake and emotional processing in healthy volunteers

et al. 2014

View full text Add to dashboard Cite

(250 words)Rationale: The treatment of obesity is an increasing global health priority yet few effective drug treatments are currently available. The discovery of novel anti-obesity therapies could be assisted by the validation of experimental (translational) medicine models in healthy volunteers that assess efficacy and safety at an early stage of drug development. Objectives:To examine the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) in an experimental medicine model assessing both appetite and mood. Methods: Using a between-subjects double blind placebo controlled design, 24 male and 24 female participants were randomly assigned to either placebo, 15mg or 30mg mCPP treatment groups. Lunch was eaten from a Universal Eating Monitor (UEM) that measured eating rate and participants completed the P1vital ® Oxford Emotional Test Battery (ETB) and a series of appetite and mood ratings. Results: mCPP reduced appetite, and in females, enhanced measures of satiation. The drug also enhanced memory for emotional material in the word recall and recognition memory tasks of the ETB. Conclusions: The results provide new insight into the effects of mCPP on appetite, satiety and memory in humans. In addition, our data provide an illustration of the value of measuring changes in appetite and mood in healthy volunteers to determine the potential efficacy and safety of novel anti-obesity drugs.

show abstract

“…The challenges presented by drug development for central nervous system (CNS) indications have motivated the search for PD methodologies that readily translate from preclinical models to patients and predict clinical efficacy [21]. Preclincal studies use transgenic or inducible rodent models of disease and in vitro studies that serve to characterize the pharmacologic properties and predicted clinical effects of a novel molecule [22–25].…”

Section: Introduction and Scopementioning

confidence: 99%

The role of fMRI in drug development

Carmichael

Schwarz

Chatham

et al. 2018

Drug Discovery Today

View full text Add to dashboard Cite

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.

show abstract

Validation of experimental medicine methods in psychiatry: The P1vital approach and experience

Cited by 14 publications

References 35 publications

Serotonin controlling feeding and satiety

Serotonin controlling feeding and satiety

Effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine on appetite, food intake and emotional processing in healthy volunteers

The role of fMRI in drug development

Contact Info

Product

Resources

About