Novel non-indolic melatonin receptor agonists differentially entrain endogenous melatonin rhythm and increase its amplitude

Drijfhout, W. J.; Vries, J. B. De; Homan, Evert; Brons, H.F; Copinga, Swier; Gruppen, Gert; Beresford, I.J.M.; Hagan, R.M.; Grol, Cor J.; Westerink, Ben H.C.

doi:10.1016/s0014-2999(99)00619-6

Cited by 9 publications

(4 citation statements)

References 31 publications

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“…Young hamsters are entrainable by daily acute Mel administration while, in the adult, Mel is not able to entrain (Davis and Manion 1988;Grosse et al 1996;Hastings et al 1992) or can entrain only under particular experimental conditions (e.g., long-term infusions) (Kirsch et al 1993;Schulher et al 2002). Moreover, a Mel receptor antagonist blocks the phase-advancing effect of Mel (Weibel et al 1999;Hunt et al 2001) and after administration of various Mel receptor agonists (Drijfhout et al 1999) an increase in the amplitude of the nocturnal Mel peak is also observed.…”

Section: Suprachiasmatic Nuclei and Melatonin Receptorsmentioning

confidence: 99%

The chronobiotic properties of melatonin

Pévet¹,

Bothorel²,

Slotten³

et al. 2002

Cell Tissue Res

137

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In mammals, the exact role of melatonin (Mel) in the circadian timing system remains to be determined. However, exogenously administered Mel, as reported in the present mini-review, has been shown to affect the circadian clock. The sites and mechanisms of action involved in this "chronobiotic" effect of Mel have begun to be characterized. The suprachiasmatic nuclei (SCN) appear to be an important site for the entrainment effect of Mel and the presence of Mel receptors appears to be a prerequisite. However, the pharmacological dose of Mel needed to entrain circadian rhythms means that very probably other sites and mechanisms also play a role.

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Section: Suprachiasmatic Nuclei and Melatonin Receptorsmentioning

confidence: 99%

The chronobiotic properties of melatonin

Pévet¹,

Bothorel²,

Slotten³

et al. 2002

Cell Tissue Res

137

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“…Drijfhout et al tested several compounds for melatonin receptor agonism. 58 GG-012 (compound 41, Fig. 9) was a partial agonist with high binding affinity (K i = 9.5 nM) for the chicken retina melatonin receptors, fivefold higher than its tetralin analog.…”

Section: Melatonin Receptorsmentioning

confidence: 97%

“…Drijfhout et al. tested several compounds for melatonin receptor agonism . GG‐012 (compound 41 , Fig.…”

Section: Targets In Diseases Of the Central Nervous System (Cns)mentioning

confidence: 99%

Indanes—Properties, Preparation, and Presence in Ligands for G Protein Coupled Receptors

Vilums

Heuberger

Heitman

et al. 2015

Medicinal Research Reviews

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The indane (2,3-dihydro-1H-indene) ring system is an attractive scaffold for biologically active compounds due to the combination of aromatic and aliphatic properties fused together in one rigid system. This bicyclic structure provides a wide range of possibilities to incorporate specific substituents in different directionalities, thus being an attractive scaffold for medicinal chemists. Notably, many indane-based compounds are being used in the clinic to treat various diseases, such as indinavir, an HIV-1 protease inhibitor; indantadol, a potent Monoamine Oxidase (MAO)-inhibitor; the amine uptake inhibitor indatraline; and the ultra-long-acting β-adrenoceptor agonist indacaterol. Given the diversity of targets these drugs act on, one could argue that the indane ring system is a privileged substructure. In the present review, the synthetic and medicinal chemistry of the indane ring system is described. In more detail, it contains a comprehensive overview of compounds bearing the indane substructure with G protein coupled receptor (GPCR) activity, with particular emphasis on their structure-activity relationships (SAR).

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“…Before experimentation, animals were housed in a temperature controlled room (21 AE 2 C) and maintained in a reversed 12 h light/12 h dark cycle (LD 12:12; lights off from 10:00 to 22:00) during 3 weeks (Barassin et al, 1999;Bothorel et al, 2002;Drijfhout et al, 1999;Hillegaart & Ahlenius, 1994;Sage et al, 2004) to adapt to the microdialysis conditions (collection of nocturnal samples of MLT). Food and water were available ad libitum.…”

Section: Animalsmentioning

confidence: 99%

Like melatonin, agomelatine (S20098) increases the amplitude of oscillations of two clock outputs: melatonin and temperature rhythms

Castanho

Bothorel

Seguin

et al. 2013

Chronobiology International

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Depression and biological rhythms disturbances are strongly associated. Agomelatine is an antidepressant with melatoninergic MT1-MT2 agonist and serotoninergic 5-HT2c antagonist properties. Both melatonin and 5-HT are known to modulate circadian rhythmicity controlled by the endogenous clock located in the suprachiasmatic nuclei (SCN). The aim of the present study was to compare the effect of an acute injection of agomelatine (Ago), melatonin (MLT) or an antagonist 5-HT2c (S32006), on the rhythms of two robust clock outputs: the pineal MLT secretion and the body temperature rhythm (Tc). Daily endogenous MLT profiles were measured using transpineal microdialysis over 4 consecutive days in rats maintained on a 12 h light/12 h dark cycle. Simultaneously, Tc was recorded. The drugs were injected subcutaneously at three doses (1, 2.5 or 5 mg/kg) at the onset of darkness. Both Ago and MLT, at the dose of 2.5 mg/kg, increased the amplitude of the peak of MLT secretion and this effect was observed 2 d after injection. Moreover, both drugs induced a dose-dependent advance of the rhythm onset which resulted in lengthening of the MLT peak. S32006 had no effect on the rhythm of MLT. Ago, MLT and S32006 increased the amplitude of the rhythm of Tc. These data suggest a central action of Ago, directly on the SCN, via melatoninergic receptors responsible for both the increased amplitude of MLT rhythm and the phase advance. The increase in the amplitude of the body temperature could involve both MLT agonist and/or 5-HT2c antagonist properties of Ago.

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Novel non-indolic melatonin receptor agonists differentially entrain endogenous melatonin rhythm and increase its amplitude

Cited by 9 publications

References 31 publications

The chronobiotic properties of melatonin

The chronobiotic properties of melatonin

Indanes—Properties, Preparation, and Presence in Ligands for G Protein Coupled Receptors

Like melatonin, agomelatine (S20098) increases the amplitude of oscillations of two clock outputs: melatonin and temperature rhythms

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