"目錄號(hào): HY-14557
GPCR/G ProteinNeuronal Signaling-
Pimavanserin 是一種有效的5-hydroxytryptamine (5-HT)2A受體反向激動(dòng)劑任斋，在細(xì)胞功能測(cè)定受體選擇和擴(kuò)增技術(shù) (R-SAT) 中激捏，具有有效的反向激動(dòng)劑活性匀归，平均pIC50為 8.7晚顷。
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生物活性
Description
Pimavanserin is a potent5-hydroxytryptamine (5-HT)2Areceptor inverse agonist, displays potent inverse agonist activity in the cell-based functional assay receptor selection and amplification technology (R-SAT), with a meanpIC50of 8.7.
IC50& Target
pIC50: 8.7 (5-HT2A)[1]
In Vitro
Pimavanserin (ACP-103) competitively antagonizes the binding of [3H]ketanserin to heterologously expressed human 5-HT2Areceptors with a mean pKiof 9.3 in membranes and 9.70 in whole cells. Pimavanserin demonstrates lesser affinity (mean pKiof 8.80 in membranes and 8.00 in whole cells, as determined by radioligand binding) and potency as an inverse agonist (mean pIC507.1 in R-SAT) at human 5-HT2Creceptors, and lacked affinity and functional activity at 5-HT2Breceptors, dopamine D2receptors, and other human monoaminergic receptors[1]. Pimavanserin (ACP-103) is highly selective for 5-HT2Areceptors, lacking affinity for other receptors in a broad profile screen including 65 different molecular targets; the only other receptor for which Pimavanserin demonstrates affinity is 5-HT2C, and Pimavanserin is approximately 30-fold selective for 5-HT2Areceptors over 5-HT2Creceptors depending on the assay[2].
In Vivo
Pimavanserin (ACP-103) is a potent, efficacious, orally active 5-HT2Areceptor inverse agonist with a behavioral pharmacological profile consistent with utility as an antipsychotic agent. Pimavanserin attenuates head-twitch behavior (3 mg/kg p.o.), and prepulse inhibition deficits (1-10 mg/kg s.c.) induced by the 5-HT2Areceptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride in rats and reduces the hyperactivity induced in mice by the N-methyl-D-aspartate receptor noncompetitive antagonist 5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate; MK-801) (0.1 and 0.3 mg/kg s.c.; 3 mg/kg p.o.), consistent with a 5-HT2Areceptor mechanism of action in vivo and antipsychotic-like efficacy. Pimavanserin demonstrates >42.6% oral bioavailability in rats[1].
Clinical Trial
ACADIA Pharmaceuticals Inc.
Parkinson's Disease Psychosis
July 2007
Phase 3
ACADIA Pharmaceuticals Inc.
Schizophrenia
August 2005
Phase 2
ACADIA Pharmaceuticals Inc.
Parkinson's Disease Psychosis
June 2007
Phase 3
ACADIA Pharmaceuticals Inc.
Hallucinations-Psychoses-Parkinson's Disease
March 2004
Phase 2
ACADIA Pharmaceuticals Inc.
Parkinson's Disease Psychosis
March 2008
Phase 3
ACADIA Pharmaceuticals Inc.
Parkinson's Disease Psychosis
November 2004
Phase 2
National Institute of Neurological Disorders and Stroke (NINDS)-National Institutes of Health Clinical Center (CC)
Parkinson's Disease-Dyskinesias
June 25, 2004
Phase 2
ACADIA Pharmaceuticals Inc.
Parkinson's Disease Psychosis
July 2007
Phase 3
ACADIA Pharmaceuticals Inc.
Schizophrenia
August 2005
Phase 2
ACADIA Pharmaceuticals Inc.
Parkinson's Disease Psychosis
June 2007
Phase 3
ACADIA Pharmaceuticals Inc.
Hallucinations-Psychoses-Parkinson's Disease
March 2004
Phase 2
ACADIA Pharmaceuticals Inc.
Parkinson's Disease Psychosis
March 2008
Phase 3
ACADIA Pharmaceuticals Inc.
Parkinson's Disease Psychosis
November 2004
Phase 2
National Institute of Neurological Disorders and Stroke (NINDS)-National Institutes of Health Clinical Center (CC)
Parkinson's Disease-Dyskinesias
June 25, 2004
Phase 2
ACADIA Pharmaceuticals Inc.
Schizophrenia
December 2016
Phase 3
ACADIA Pharmaceuticals Inc.
Agitation and Aggression in Alzheimer's Disease
February 23, 2017
Phase 2
ACADIA Pharmaceuticals Inc.
Alzheimer's Disease Psychosis
November 2013
Phase 2
ACADIA Pharmaceuticals Inc.
Parkinson's Disease Psychosis
July 2010
Phase 3
ACADIA Pharmaceuticals Inc.
Schizophrenia
October 2016
Phase 3
ACADIA Pharmaceuticals Inc.
Schizophrenia
November 2016
Phase 2
ACADIA Pharmaceuticals Inc.
Adjunctive Treatment of Major Depressive Disorder
December 2016
Phase 2
ACADIA Pharmaceuticals Inc.
Agitation and Aggression in Alzheimer's Disease
November 2016
Phase 2
ACADIA Pharmaceuticals Inc.
Parkinson's Disease Psychosis
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References
