Pimavanserin
Grundinformationen
- CAS
706779-91-1- Standard-SMILES
CC(C)COc1ccc(CNC(=O)N(Cc2ccc(F)cc2)C2CCN(C)CC2)cc1- InChIKey
RKEWSXXUOLRFBX-UHFFFAOYSA-N- Summenformel
- C25H34FN3O2
- Durchschnittliche Molmasse
- 427,6 g/mol
- Monoisotopische Masse
- 427,2635055
Überblick
Pimavanserin is a member of the class of ureas in which three of the four hydrogens are replaced by 4-fluorobenzyl, 1-methylpiperidin-4-yl, and 4-(isopropyloxy)benzyl groups. An atypical antipsychotic that is used (in the form of its tartrate salt) for treatment of hallucinations and delusions associated with Parkinson's disease. It has a role as a 5-hydroxytryptamine 2A receptor inverse agonist, an antipsychotic agent and a serotonergic antagonist. It is a member of piperidines, an aromatic ether, a member of ureas, a tertiary amino compound and a member of monofluorobenzenes. It is a conjugate base of a pimavanserin(1+).
Namen und Bezeichner
- Bevorzugter Name
- Pimavanserin
- IUPAC
- 1-[(4-fluorophenyl)methyl]-1-(1-methylpiperidin-4-yl)-3-[[4-(2-methylpropoxy)phenyl]methyl]urea
- Englischer Name
- Pimavanserin
- Summenformel
- C25H34FN3O2
- Molmasse
- 427.55
Namen und Synonyme
Pimavanserin706779-91-1ACP-103pimavanserinapimavanserineJZ963P0DIKCHEBI:133017DTXSID909909061-[(4-fluorophenyl)methyl]-1-(1-methylpiperidin-4-yl)-3-[[4-(2-methylpropoxy)phenyl]methyl]ureaN-(4-Fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamideACP 103N-(4-Fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl)carbamide
Weitere Namen anzeigen
Pimavanserin-d4PimaserinPimvanserinPimofanerolPimavamserinPimanavserinUnii-jz963p0dikD4-Pimavanserin
1-[(4-fluorophenyl)methyl]-1-(1-methylpiperidin-4-yl)-3-{[4-(2-methylpropoxy)phenyl]methyl}ureapimavanserinum1-((4-fluorophenyl)methyl)-1-(1-methylpiperidin-4-yl)-3-((4-(2-methylpropoxy)phenyl)methyl)ureaRefChem:59074ACP103DTXCID70206052N05AX171-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-1-(1-methylpiperidin-4-yl)urea
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- 4,5
- Polarare Oberfläche (TPSA)
- 44,8 Ų
- H-Brücken-Donoren
- 1
- H-Brücken-Akzeptoren
- 4
- Frei drehbare Bindungen
- 8
- Schwere Atome
- 31
- Formalladung
- 0
- Komplexität
- 523
Experimentelle und physikochemische Eigenschaften
Drugs
Pharmaceuticals -> Listed in ZINC15
Pharmaceuticals -> Nervous system -> Antipsychotics
Human DrugsBreast Feeding; Lactation; Milk, Human; Antiparkinson Agents; Antipsychotic Agents; Serotonin 5-HT2 Receptor Antagonists
Boiling Point604.2±55.0
Melting Point117-119
Dissociation Constants13.52±0.46
Physikochemische Eigenschaften
- Schmelzpunkt
- 100 · 100-103oC
- Siedepunkt
- 604.2 · 604.2±55.0 °C(Predicted)
- Dichte
- 1.15 · 1.15±0.1 g/cm3(Predicted)
- storage temp.
- Refrigerator
- Löslichkeit
- Methanol (Slightly)
- pka
- 13.52 · 13.52±0.46(Predicted)
Sicherheit und Regulatorisches
Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.
Toxikologische Informationen
HepatotoxicityLiver test abnormalities are uncommon (
Adverse Effects
In the controlled trial setting, common adverse effects at an incidence of 5% or more included peripheral edema, confusional state, and nausea. Adverse reactions at an incidence of 2% or greater included hallucinations, peripheral edema, nausea, confusion, constipation, and gait disturbances. Instances in which treatment was discontinued in patients treated with pimavanserin (8%), as well as patients treated with placebo (4%), included hallucinations (2% pimavanserin 34 mg versus less than 1% placebo), urinary tract infection (1% pimavanserin 34 mg versus less than 1% placebo), and fatigue (1% pimavanserin 34 mg versus 0% placebo).
Toxicity SummaryThere have been no reported overdoses to date, and there is no specific antidote for pimavanserin.
Effects During Pregnancy and Lactation◉ Summary of Use during Lactation
Sicherheitsdaten
- wgk
- WGK 2
- hs_code
- 29339900
- hazard_code
- Xi
- safety_code
- 24/25
- Speicherklasse
- 3 - Flammable liquids
- Hazard Classifications
- Acute Tox. 4 DermalAcute Tox. 4 InhalationAcute Tox. 4 OralEye Irrit. 2Flam. Liq. 2
Chemie und Industrie
Pharmakologische Informationen
ATC Code
N - Nervous system
QN - Nervous system
Protein BindingPimavanserin is highly protein-bound (~95%) in human plasma. Protein binding appeared to be dose-independent and did not change significantly over dosing time from Day 1 to Day 14.
Pharmacodynamics
Pimavanserin's unique actions on serotonin receptors improve symptoms of hallucinations and delusions associated with Parkinson's disease. In clinical studies, 80.5% of individuals treated with pimavanserin reported improvement in symptoms. Pimavanserin does not worsen motor functioning in patients with Parkinson's disease psychosis. In vitro, pimavanserin acts as an inverse agonist and antagonist at serotonin 5-HT<sub>2A</sub> receptors with high binding affinity (K<sub>i</sub> value 0.087 nM) and at serotonin 5-HT<sub>2C</sub> receptors with lower binding affinity (K<sub>i</sub> value 0.44 nM). Pimavanserin shows low binding to sigma 1 receptors (K<sub>i</sub> value 120 nM) and has no appreciable affinity (K<sub>i</sub> value >300 nM), to serotonin 5-HT<sub>2B</sub>, dopaminergic (including D<sub>2</sub>), muscarinic, histaminergic, or adrenergic receptors, or to calcium channels. The effect of pimavanserin on the QTc interval was evaluated in a randomized placebo- and positive-controlled double-blind, multiple-dose parallel thorough QTc study in 252 healthy subjects. A central tendency analysis of the QTc data at steady-state demonstrated that the maximum mean change from baseline (upper bound of the two-sided 90% CI) was 13.5 (16.6) msec at a dose of twice the therapeutic dose. A pharmacokinetic/pharmacodynamic analysis with pimavanserin suggested a concentration-dependent QTc interval prolongation in the therapeutic range. In the 6-week, placebo-controlled effectiveness studies, mean increases in QTc interval of ~5-8 msec were observed in patients receiving once-daily doses of pimavanserin 34 mg. These data are consistent with the profile observed in a thorough QT study in healthy subjects. Sporadic QTcF values ≥500 msec and change from baseline values ≥60 msec were observed in subjects treated with pimavanserin 34 mg; although the incidence was generally similar for pimavanserin and placebo groups. There were no reports of torsade de pointes or any differences from placebo in the incidence of other adverse reactions associated with delayed ventricular repolarization in studies of pimavanserin, including those patients with hallucinations and delusions associated with Parkinson’s disease psychosis.
Zugehörige Reaktionen
0
Keine Reaktionsaufzeichnungen unter den aktuellen Filterkriterien.
Notizen zur Verbindung
Wird geladen…