The brain H3-receptor as a novel therapeutic target for vigilance and sleep–wake disorders

Parmentier, Régis; Anaclet, Christelle; Guhennec, C.; Brousseau, Emmanuel; Bricout, Denis; Giboulot, Thierry; Bozyczko–Coyne, Donna; Spiegel, Karine; Ohtsu, Hiroshi; Williams, Michael; Lin, Jian‐Sheng

doi:10.1016/j.bcp.2007.01.002

Cited by 156 publications

(120 citation statements)

References 57 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…Both tiprolisant and modafinil enhanced wakefulness during the lights-off (active) period in orexin-/-mice, as is observed in WT rodents (Scammell et al,2000;Parmentier et al,2007;Ligneau et al,2007b) and cats (Lin et al,1992;Ligneau et al,1998Ligneau et al, ,2007a.…”

Section: Discussionmentioning

confidence: 61%

“…Similarly, modafinil-induced waking was accompanied with c-fos labeling in the tuberomammillary nucleus but not the locus coeruleus in rats (Scammell et al,2000) and its arousal-promoting action did not involve the presynaptic noradrenergic system in cats and mice (Lin et al,1992;Wisor and Eriksson, 2005). Nevertheless, the change in t-MeHA was of modest amplitude and the wake-promoting effect of modafinil is unaffected in mice KO for the gene of the HA-synthesizing enzyme (Parmentier et al,2007).…”

Section: Discussionmentioning

confidence: 93%

“…The wake-promoting effect of modafinil does not depend on the HA-mediated transmission (Parmentier et al,2007). Hence, it would activate histaminergic neurons in a way distinct from that of tiprolisant.…”

Section: Discussionmentioning

confidence: 95%

“…Modafinil, a currently-prescribed wake-promoting drug with distinct mechanisms of action from those of H3 receptor inverse agonists (Parmentier et al,2007), was used for comparison and co-administration with tripolisant. We found that modafinil enhanced tMeHA levels to a lesser extent than tiprolisant and that it did not significantly affect MHPG/NA ratio.…”

Section: Discussionmentioning

confidence: 99%

“…This class of agents is known to promote wakefulness by inhibiting the constitutively active H3-autoreceptor, thereby enhancing histaminergic neuron activity and histamine (HA) release (Schwartz et al, 1991;Lin, 2000;Morisset et al, 2000;Vanni-Mercier et al, 2003;Parmentier et al, 2002Parmentier et al, , 2007.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy: Studies in orexin−/− mice and patients

Lin

Dauvilliers

Arnulf

et al. 2008

Neurobiology of Disease

249

178

View full text Add to dashboard Cite

Abbreviations AbstractNarcolepsy is characterized by excessive daytime sleepiness(EDS), cataplexy, direct onsets of rapid eye movement(REM) sleep from wakefulness(DREMs) and deficiency of orexins, neuropeptides that promote wakefulness largely via activation of histamine (HA) pathways. The hypothesis that the orexin defect can be circumvented by enhancing HA release was explored in narcoleptic mice and patients using tiprolisant, an inverse H3-receptor agonist. In narcoleptic orexin-/-mice, tiprolisant enhanced HA and noradrenaline neuronal activity, promoted wakefulness and decreased abnormal DREMs, all effects being amplified by co-administration of modafinil, a currently prescribed wake-promoting drug. In a pilot single-blind trial on 22 patients receiving a placebo followed by tiprolisant, both for one week, the Epworth Sleepiness Scale(ESS) score was reduced from a baseline value of 17.6 by 1.0 with the placebo(p>0.05) and 5.9 with tiprolisant(p<0.001). Excessive daytime sleep, unaffected under placebo, was nearly suppressed on the last days of tiprolisant-dosing. H3-receptor inverse agonists could constitute a novel effective treatment of EDS, particularly when associated with modafinil.

show abstract

Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy: Studies in orexin−/− mice and patients

Lin

Dauvilliers

Arnulf

et al. 2008

Neurobiology of Disease

249

178

View full text Add to dashboard Cite

show abstract

Rational Modification of the Biological Profile of GPCR Ligands through Combination with Other Biologically Active Moieties

Huang

Nimczick

Decker

2015

Archiv der Pharmazie

View full text Add to dashboard Cite

In recent years, G protein-coupled receptor (GPCR) ligands have not only been modified by conducting structure-activity relationship studies of leads and known ligands, but several new approaches have emerged in which GPCR ligands were connected or merged with other biologically active molecules. Identical or related ligands were combined to bivalent ones. Orthosteric ligands were combined with allosteric ligands, sometimes leading to dualsteric ones, and also chemical structures were merged to dual-acting or multifunctional compounds. In this article, we want to present some representative examples for these approaches at different GPCRs, showing the versatility of this approach, with a focus on our own work and references to related articles and reviews.

show abstract

Approaches to measuring the effects of wake‐promoting drugs: a focus on cognitive function

Edgar¹,

Pace‐Schott

Wesnes³

2009

Human Psychopharmacology

View full text Add to dashboard Cite

Objectives In clinical drug development, wakefulness and wake-promotion maybe assessed by a large number of scales and questionnaires. Objective assessment of wakefulness is most commonly made using sleep latency/maintenance of wakefulness tests, polysomnography and/or behavioral measures. The purpose of the present review is to highlight the degree of overlap in the assessment of wakefulness and cognition, with consideration of assessment techniques and the underlying neurobiology of both concepts. Design Reviews of four key areas were conducted: commonly used techniques in the assessment of wakefulness; neurobiology of sleep/wake and cognition; targets of wake promoting and/or cognition enhancing drugs; and ongoing clinical trials investigating wake promoting effects. Results There is clear overlap between the assessment of wakefulness and cognition. There are common techniques which may be used to assess both concepts; aspects of the neurobiology of both concepts may be closely related; and wake promoting drugs may have nootropic properties (and vice-versa). Clinical trials of wake promoting drugs often, though not routinely, assess aspects of cognition. Conclusions Routine and broad assessment of cognition in the development of wake promoting drugs may reveal important nootropic effects, which are not secondary to alertness/wakefulness, whilst existing cognitive enhancers may have under explored or unknown wake promoting properties.

show abstract

The brain H3-receptor as a novel therapeutic target for vigilance and sleep–wake disorders

Cited by 156 publications

References 57 publications

An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy: Studies in orexin−/− mice and patients

An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy: Studies in orexin−/− mice and patients

Rational Modification of the Biological Profile of GPCR Ligands through Combination with Other Biologically Active Moieties

Approaches to measuring the effects of wake‐promoting drugs: a focus on cognitive function

Contact Info

Product

Resources

About