Agomelatine

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H400：Sehr giftig für Wasserorganismen.

• Sicherheit

  P273：Freisetzung in die Umwelt vermeiden.

Agomelatine Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  Agomelatine is an agonist of melatonin (MT) receptors and a derivative of melatonin . It binds to MT₁ and MT₂ receptors (K_is = 0.14 and 0.41 nM, respectively) and has an EC₅₀ value of 0.1 nM in a [³⁵S]GTPγS binding assay using CHO cells expressing MT₂ receptors. Agomelatine is also an antagonist of the serotonin (5-HT) receptor subtypes 5-HT_2B and 5-HT_2C (K_is = 0.26 and 0.71 nM, respectively, for the human receptors). Agomelatine (40 mg/kg) inhibits the penile erection response induced by the 5-HT₂ agonist Ro 60-0175 in rats. It also increases extracellular levels of noradrenaline and dopamine in the frontal cortex of freely moving rats when administered at doses ranging from 20 to 80 mg/kg. Agomelatine (10 mg/kg) reduces immobility time in the forced swim test and increases the amount of time spent in the open arms of the elevated plus maze in mice, indicating antidepressant-like and anxiolytic-like activity, in a transgenic neuroendocrine model of depression. It also increases the rate of readjustment to circadian activity cycles following an induced phase shift.

• Chemische Eigenschaften

  White Solid

• Verwenden

  Agomelatine is a melatoninergic agonist and selective antagonist of 5-HT2C receptors, and has been shown to be active in several animal models of depression. Agomelatine (S20098) displayed pKi values of 6.4 and 6.2 at native (porcine) and cloned, human (h)5-hydroxytryptamine (5-HT)2C receptors, respectively.

• Verwenden

  Agomelatine has been used:
  
  • to study its effects on adult neurogenesis and hippocampus apoptosis using the stress-induced depression model of rats
  • to explore its effects on tau protein phosphorylation and to study its neuroprotective mechanism
  • to study its effects on intracellular calcium ([Ca²⁺]i) signaling in peripheral neurons of rat dorsal root ganglion (DRG) neurons
  
  

• Verwenden

  Agomelatine is an antidepressant drug. It is classified as a norepinephrine-dopamine disinhibitor (NDDI) due to its antagonism of the 5-HT2C receptor. Activation of 5-HT2C receptors by serotonin inhibits dopamine and norepinephrine release. Antagonism of

• Definition

  ChEBI: Agomelatine is a member of acetamides.

• Biochem/physiol Actions

  Agomelatine is an extremely potent agonist at both melatonin receptors (MT1 and MT2), with additional antagonism at 5HT2C. It is a novel antidepressant with many desired in vivo properties, including neuroprotection and neurogenesis in depression-sensitive brain areas. Agomelatine′s efficacy appears to be due to both melatonergic and serotonergic properties. In neurogenesis assays, both in vitro and in vivo, the compound effects were differentially affected by antagonists for MT1/MT2 and 5HT2C, demonstrating actions through all three receptors.

• Clinical Use

  Antidepressant

• target

  TNF-α | IL Receptor | P450 (e.g. CYP17) | 5-HT Receptor

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Antibacterials: avoid with ciprofloxacin.
  Antidepressants: metabolism inhibited by fluvoxamine.
  Antimalarials: avoid with artemether with lumefantrine and artenimol with piperaquine.

• Stoffwechsel

  Agomelatine is rapidly metabolised, mainly by the hepatic cytochrome P450 isoenzyme CYP1A2; the isoenzymes CYP2C9 and CYP2C19 also make a minor contribution. The major metabolites, hydroxylated and demethylated agomelatine, are not active and are rapidly conjugated and eliminated in the urine.

• Einzelnachweise

  [1] zupancic m, guilleminault c. agomelatine. cns drugs, 2006, 20(12): 981-992.

Agomelatine Upstream-Materialien And Downstream Produkte

Agomelatine Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(624)Suppliers

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