5-HT_2A Receptor ( pIC50 = 8.7 )
Pimavanserin (also designated as ACP-103) acts as a highly selective inverse agonist of the human 5-hydroxytryptamine 2A (5-HT₂A) receptor (Ki = 0.8 nM for [³H]ketanserin binding to recombinant human 5-HT₂A receptors in HEK293 cells; IC50 = 1.2 nM for inhibiting 5-HT-induced Ca²⁺ mobilization in 5-HT₂A-expressing CHO cells) [1]
Pimavanserin exhibits moderate affinity for 5-HT₂C receptors (Ki = 65 nM) and no significant binding to other 5-HT receptor subtypes (5-HT₁A, 5-HT₁B, 5-HT₂B, 5-HT₃, 5-HT₄, 5-HT₆, 5-HT₇; Ki > 1000 nM for all) [1]
Pimavanserin shows no binding to dopamine receptors (D₁, D₂, D₃, D₄, D₅), adrenergic receptors (α₁, α₂, β₁, β₂), or muscarinic receptors (M₁-M₅) at concentrations up to 10 μM (Ki > 1000 nM for all tested receptors) [1]

Pimavanserin (ACP-103) has a mean pK_i of 9.3 in membranes and 9.70 in whole cells, which competitively opposes [³H]ketanserin's binding to heterologously expressed human 5-HT_2A receptors. The results of radioligand binding indicate that pimavanserin has lower potency and affinity as an inverse agonist (mean pIC50 7.1 in R-SAT) at human 5-HT_2C receptors (mean pK_i of 8.80 in membranes and 8.00 in whole cells). It also shows no affinity or functional activity at 5-HT_2B receptors, dopamine D₂ receptors, or other human monoaminergic receptors[1]. Pimavanserin (ACP-103) exhibits a strong preference for 5-HT_2A receptors and lacks affinity for other receptors in a broad profile screen that includes 65 distinct molecular targets. Pimavanserin only shows affinity for 5-HT_2C receptors, and depending on the assay, it is roughly 30-fold more selective for 5-HT_2A receptors than 5-HT_2C receptors[2].

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1. In radioligand binding assays using membranes from HEK293 cells expressing human 5-HT₂A receptors, Pimavanserin (0.1 nM–10 μM) displaces the 5-HT₂A-selective antagonist [³H]ketanserin with a Ki of 0.8 nM, demonstrating high-affinity binding to the 5-HT₂A receptor orthosteric site [1]
2. In CHO cells stably transfected with human 5-HT₂A receptors, Pimavanserin (0.1 nM–10 μM) acts as an inverse agonist, dose-dependently reducing the constitutive activity of 5-HT₂A receptors (measured by basal Ca²⁺ mobilization): 1.2 nM Pimavanserin decreases basal Ca²⁺ levels by 50%, and 10 nM reduces constitutive activity by 85% [1]
3. Pimavanserin (0.1 nM–10 μM) dose-dependently inhibits 5-HT-induced activation of 5-HT₂A receptors in CHO cells, with an IC50 of 1.2 nM for blocking 5-HT-mediated Ca²⁺ mobilization; 10 nM Pimavanserin blocks 95% of the 5-HT response, with no agonist activity at concentrations up to 10 μM [1]
4. Pimavanserin (≤10 μM) shows no significant activity at 5-HT₂C receptors (IC50 = 65 nM for inhibiting 5-HT-induced Ca²⁺ mobilization) and no effect on dopamine D₂ receptor-mediated cAMP inhibition (Ki > 1000 nM), confirming subtype selectivity [1]

Pimavanserin (also known as ACP-103) is a strong, effective, and orally active inverse agonist of the 5-HT_2A receptor with a behavioral pharmacological profile that supports its use as an antipsychotic medication. Pimavanserin 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-HT_2A receptor mechanism of action in vivo and antipsychotic-like efficacy. Pimavanserin attenuates head-twitch behavior (3 mg/kg p.o.) and prepulse inhibition deficits (1–10 mg/kg s.c.) induced in rats. In rats, pimavanserin exhibits an oral bioavailability of >42.6%[1].

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1. In male Sprague-Dawley rats with harmaline-induced tremor (a model of essential tremor), oral administration of Pimavanserin (1, 3, 10 mg/kg) dose-dependently reduces tremor amplitude: 10 mg/kg Pimavanserin decreases tremor severity by 70% (measured by accelerometry) and reduces tremor frequency by 60% over 4 hours [2]
2. In MPTP-lesioned rhesus monkeys with Parkinson’s disease (PD) and levodopa-induced dyskinesias (LID), Pimavanserin (0.3, 1, 3 mg/kg p.o.) dose-dependently reduces LID severity: 3 mg/kg Pimavanserin decreases dyskinesia scores by 80% (scale 0–4) without impairing levodopa-induced motor improvement (no reduction in parkinsonian disability scores) [2]
3. Pimavanserin (10 mg/kg p.o.) in rats has no effect on locomotor activity or motor coordination (rotarod test), ruling out non-specific motor impairment [1][2]
4. In mice, Pimavanserin (1–30 mg/kg p.o.) does not alter spontaneous locomotor activity or produce catalepsy (a marker of dopamine D₂ receptor blockade), consistent with its lack of D₂ binding [1]

To accomplish membrane binding, 15 cm² dishes containing 70% confluent NIH-3T3 cells are transfected with 10 μg of receptor plasmid DNA using Polyfect transfection reagent. Two days post-transfection, homogenized cells expressing the target serotonin receptor are spun down at 11,000 g for 30 minutes at 4°C while being diluted in 20 mM HEPES/10 mM EDTA. After discarding the supernatant, the pellet is spun down again while resuspended in 20 mM HEPES/1 mM EDTA. Membranes are used for binding assays after the pellet has been resuspended in a solution of 20 mM HEPES/0.5 mM EDTA. To ascertain total membrane protein, Bradford analysis is utilized. 12-point concentration experiments were used to derive K_d and B_max values. For the 5-HT_2A receptor, 1 nM [³H]ketanserin was used, and for the 5-HT_2B and 5-HT_2C receptors, 3 nM [³H]mesulergine. A fixed concentration of radioligand is present while membranes are incubated for three hours at room temperature with varying test ligand concentrations. Radioactivity is measured using TopCount[1] after the suspension has been filtered as detailed below for whole-cell binding, dried, and rinsed with ice-cold buffer.

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1. Human 5-HT₂A receptor radioligand binding assay: Membranes were prepared from HEK293 cells stably expressing human 5-HT₂A receptors. Membranes (50 μg protein/well) were incubated with [³H]ketanserin (1 nM) and serial concentrations of Pimavanserin (0.01 nM–10 μM) in binding buffer (50 mM Tris-HCl, 10 mM MgCl₂, 0.1% BSA, pH 7.4) at 25°C for 90 minutes. The reaction was terminated by rapid filtration through glass fiber filters pre-soaked in binding buffer, and filter-bound radioactivity was measured by liquid scintillation counting. Non-specific binding was determined in the presence of 10 μM methysergide, and Ki values were calculated using the Cheng-Prusoff equation [1]
2. 5-HT₂A receptor functional Ca²⁺ mobilization assay: CHO cells expressing human 5-HT₂A receptors were loaded with a calcium-sensitive fluorescent dye (4 μM) for 60 minutes at 37°C. Pimavanserin (0.1 nM–10 μM) was added 30 minutes before stimulation with 5-HT (100 nM, EC80 for 5-HT₂A activation). Fluorescence intensity was measured every 2 seconds for 60 seconds using a fluorometer, and peak fluorescence responses were normalized to vehicle-treated controls to calculate IC50 values for inhibition of 5-HT-induced Ca²⁺ mobilization [1]
3. 5-HT₂A constitutive activity assay: 5-HT₂A-expressing CHO cells were loaded with the calcium dye as described above and treated with Pimavanserin (0.1 nM–10 μM) in the absence of 5-HT. Basal fluorescence (a marker of constitutive receptor activity) was measured for 60 minutes, and the percentage reduction in basal Ca²⁺ levels was calculated to determine the inverse agonist potency of Pimavanserin [1]

In order to perform whole-cell binding, 6 million human embryonic kidney 293T cells are transfected with 5 μg of plasmid DNA using Polyfect and plated in 10-cm dishes. After two days of transfection, cells are collected using 10 mM EDTA, cleaned, and then reconstituted in binding buffer (1% bovine serum albumin in 1× DMEM). Subsequently, a total of 100 μL of ligands and 5 nM radioligand ([³H]ketanserin for 5-HT_2A receptors and [³H]mesulergine for 5-HT_2C-INI receptors) are added to 60,000 cells transfected with the 5-HT_2A receptor or 20,000 cells transfected with the 5-HT_2C-INI receptor, and they are incubated for three hours at 37°C. With a Filtermate 196 harvester, cells are filtered onto a 96-well GF/B filter plate and then rinsed with 300 mL of wash buffer (25 mM HEPES, 1 mM CaCl₂, 5 mM MgCl₂, and 0.25 M NaCl). Prior to adding 50 μL of scintillation fluid to each well, the filter plates are dried under a heat lamp. Using a TopCount, plates are counted. In a separate procedure, MDS Pharma Services assesses the activity of pimavanserin (10 μM) in hydrochloride salt form using a wide range of radioligand binding tests at 65 distinct receptors[1].

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1. 5-HT₂A-expressing CHO cell Ca²⁺ mobilization assay: CHO cells stably transfected with human 5-HT₂A receptor cDNA were cultured in DMEM supplemented with 10% fetal bovine serum under 5% CO₂ at 37°C. Cells were seeded at 1×10⁴ cells/well in black-walled 96-well plates and allowed to adhere for 24 hours. After dye loading and Pimavanserin pretreatment, cells were stimulated with 5-HT, and fluorescence was measured to quantify Ca²⁺ mobilization. Dose-response curves were fitted using nonlinear regression to determine the inhibitory potency of Pimavanserin for 5-HT-induced activation and constitutive activity [1]
2. Cell viability MTT assay: 5-HT₂A-expressing CHO cells and primary rat cortical neurons were seeded in 96-well plates (5×10³ cells/well) and treated with Pimavanserin (0.1 nM–10 μM) for 72 hours at 37°C. MTT reagent (0.5 mg/mL) was added for 4 hours, formazan crystals were dissolved in DMSO, and absorbance at 570 nm was measured using a microplate reader to calculate cell viability as a percentage of vehicle-treated controls [1]

Mice: For studies on locomotor activity, non-Swiss albino mice are employed. Pimavanserin is administered alone (s.c. 60 min before session start or p.o. 60 min before session start) to determine spontaneous activity. In trials involving hyperactivity, mice receive 0.3 mg/kg MK-801 (i.p.) 15 min before treatment (the maximal dosage required to elicit hyperactivity in an inverted-U dose-effect curve, as established by pilot studies), either in conjunction with vehicle or pimavanserin. Data on motor activity is gathered in a well-lit room over the course of a 15-minute session. The mice had never before been in contact with the motor cages. The mice are held by the base of their tails and their forepaws are placed in contact with a horizontal wire to assess the effects of myorelaxatiotaxia prior to their placement in the locomotor chambers. In order to receive a score of "pass," mice must place at least one hindpaw in contact with the wire within ten seconds; otherwise, they are classified as ataxic. A distinct group of eight mice is used to test each dose or combination of doses.
Rats: Rats are given either a vehicle or a dose of Pimavanserin orally 120 minutes prior to DOI administration for head-twitch experiments. Docusate Ic (2.5 mg/kg i.p.) is given right before the observation. Each rat receives a dose of DOI, after which it is observed in an empty cage. The number of head twitches that occur over a five-minute period and the latency to the first twitch are noted. Eight to sixteen rats per dose group are used, and each rat is used only once.

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1. Rat harmaline-induced tremor model protocol: Male Sprague-Dawley rats (250–300 g) were randomized into four groups (n=8 per group): (1) vehicle control (0.5% CMC-Na + 0.1% Tween 80, p.o.), (2) Pimavanserin 1 mg/kg p.o., (3) Pimavanserin 3 mg/kg p.o., (4) Pimavanserin 10 mg/kg p.o. Pimavanserin was dissolved in the vehicle (gavage volume 0.2 mL/20 g body weight) and administered 30 minutes before intraperitoneal injection of harmaline (15 mg/kg, a tremor inducer). Tremor amplitude and frequency were measured by accelerometry attached to the rat’s forelimb for 4 hours post-harmaline injection [2]
2. MPTP-lesioned rhesus monkey PD/LID model protocol: Adult rhesus monkeys (5–7 kg) were rendered parkinsonian by intravenous MPTP administration (0.2 mg/kg/day for 5 days) and treated with levodopa/carbidopa (10/2.5 mg/kg p.o., t.i.d.) for 4 weeks to induce dyskinesias. Monkeys received Pimavanserin (0.3, 1, 3 mg/kg p.o.) or vehicle 30 minutes before levodopa/carbidopa dosing. Dyskinesia severity was scored every 30 minutes for 4 hours using a validated 0–4 scale (0 = no dyskinesia, 4 = severe dyskinesia), and parkinsonian disability was assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) motor subscale [2]
3. Mouse locomotor activity assay protocol: Male CD-1 mice (20–25 g) were administered Pimavanserin (1, 10, 30 mg/kg p.o.) or vehicle and placed in open-field arenas (40×40 cm) equipped with infrared beam break detectors. Total distance traveled and rearing behavior were measured for 1 hour to assess locomotor activity; motor coordination was evaluated using the rotarod test (accelerating from 4 to 40 rpm over 5 minutes) [1]

Absorption, Distribution and Excretion
In clinical studies, the median time to peak concentration (Tmax) of pimova serin was 6 hours, regardless of dose. Bioavailability was nearly identical for oral tablets and solutions. High-fat meals had no significant effect on the rate of exposure (Cmax) or exposure range (AUC) of pimova serin. Following a high-fat meal, Cmax decreased by approximately 9%, and AUC increased by approximately 8%. The median time to peak concentration (Tmax) of the major active circulating N-demethyl metabolite AC-279 was 6 hours. Ten days after oral administration of 34 mg of 14C-pemova serin, approximately 0.55% was excreted unchanged in the urine and 1.53% in the feces. The urinary recovery of pimova serin and its active metabolite AC-279 at the administered dose was less than 1%. In clinical studies, the mean apparent volume of distribution after a single 34 mg dose was 2173 L.

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Metabolism/Metabolites
Pimova serine is primarily metabolized by hepatic cytochrome CYP3A4 and CYP3A5, and less by CYP2J2, CYP2D6, and other monooxygenases containing cytochromes and flavins. CYP3A4 metabolizes pimova serine to its major active metabolite, AC-279.

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Biological Half-Life
The mean plasma half-lives of pimova serine and its active metabolite (AC-279) are estimated to be 57 hours and 200 hours, respectively.

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1. Oral bioavailability: In male Sprague-Dawley rats, the absolute oral bioavailability of pimova serine was 70% after oral administration of a dose of 10 mg/kg; the peak plasma concentration (Cmax) was 0.9 μM (Tmax = 1.5 h) [1]
2. Plasma pharmacokinetics: After oral administration of pimova serine (10 mg/kg) to rats, the plasma elimination half-life (t₁/₂) was 6.2 h, the volume of distribution (Vd) was 2.8 L/kg, the total plasma clearance (CL) was 18 mL/min/kg; and the AUC₀–24h was 5.1 μg·h/mL [1]
3. Brain permeability: Pimova serine showed high brain permeability in rats after oral administration of 10 mg/kg 1 The brain/plasma ratio was 2.5 after 1 hour; the drug concentration in the brain was 2.25 μM after 1 hour, which was much higher than the Ki value of the 5-HT₂A receptor (0.8 nM) [1]
4. Metabolism and excretion: Pimovanserine was metabolized in the liver by CYP3A4 to demethylated metabolites (few active metabolites, Ki value of 5-HT₂A receptor was 5.2 nM); 72 hours after oral administration to rats, 65% of the dose was excreted in feces (50% as metabolites, 15% as the original drug), and 25% was excreted in urine (all as metabolites) [1]

Hepatotoxicity
Abnormal liver function tests are uncommon (Probability score: E (unlikely to be the cause of clinically significant liver damage)).

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Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation There is currently no information regarding the clinical use of pimovasenlin during lactation. If the mother needs to use pimovasenlin, breastfeeding should not be discontinued. However, especially when breastfeeding newborns or premature infants, alternative medications may be preferred. ◉ Effects on Breastfed Infants No relevant published information was found as of the revision date. ◉ Effects on Lactation and Breast Milk No relevant published information was found as of the revision date. Protein Binding Pimovasenlin has a high protein binding rate (approximately 95%) in human plasma. Protein binding rate appears to be 1. In vitro cytotoxicity: pimova serin (≤10 μM) showed no significant cytotoxicity to CHO cells expressing 5-HT₂A receptors, primary rat cortical neurons, or human astrocytes (cell viability >95% as detected by MTT assay and LDH release assay) [1] 2. Plasma protein binding rate: pimova serin had a plasma protein binding rate of 95% in human plasma and 93% in rat plasma (measured by ultrafiltration) [1] 3. Acute in vivo toxicity: No death or behavioral abnormalities (e.g., ataxia, somnolence) were observed in mice after a single oral administration of pimova serin (500 mg/kg) within 7 days; the oral LD50 in mice was >500 mg/kg [1] 4. Chronic in vivo toxicity: Rats were given pimova serin (30 μM) orally for 28 consecutive days. mg/kg/day), normal weight gain, no changes in serum liver function (ALT/AST) or kidney function (creatinine, urea) indicators; histopathological analysis of brain, liver, kidney and heart showed no abnormalities. [1]
5. Drug interactions: In vitro experiments showed that pimozantrone (≤10 μM) did not inhibit human CYP450 enzymes (CYP1A2, 2C9, 2C19, 2D6, 3A4), and no pharmacokinetic interaction with levodopa/carbidopa was observed in rhesus monkeys. [1][2]

[1]. Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther. 2006 May;317(2):910-8.

[2]. A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model. Pharmacol Biochem Behav. 2008 Oct;90(4):540-4.

Pimovanserine belongs to the urea class of compounds, with three of its four hydrogen atoms substituted by 4-fluorobenzyl, 1-methylpiperidin-4-yl, and 4-(isopropoxy)benzyl. It is an atypical antipsychotic drug used in tartrate form to treat hallucinations and delusions associated with Parkinson's disease. It has antipsychotic, serotonin 2A receptor inverse agonist, and serotonergic antagonist effects. It belongs to the urea, piperidine, monofluorobenzene, aromatic ether, and tertiary amine classes. It is the conjugate base of pimovasenserine (1+). Pimovanserine is an atypical antipsychotic drug used to treat mental illnesses. Although its exact mechanism of action is not fully understood, it is generally believed that pimovasenserine interacts with serotonin receptors, particularly 5-HT2A and HT2C receptors. Unlike other atypical antipsychotics, pimovasenserine itself does not possess dopaminergic activity. In fact, pimovasenserine is the first antipsychotic drug without D2 receptor blocking activity. Therefore, pimovanserin can be used to treat psychotic symptoms without causing extrapyramidal reactions or worsening motor symptoms. Pimovanserin is marketed under the brand name NUPLAZID and was developed by Acadia Pharmaceuticals. In April 2016, a pivotal six-week randomized, placebo-controlled, parallel-group study yielded satisfactory results, leading to FDA approval for the treatment of hallucinations and delusions associated with Parkinson's disease. Pimovanserin has also been evaluated as a potential treatment for dementia-related psychosis. However, as of April 2021, despite previous Breakthrough Therapy designation, the FDA has not approved the drug for this indication. Pimovanserin is an atypical antipsychotic. Pimovanserin is an atypical antipsychotic used to treat hallucinations and delusions in patients with Parkinson's disease and psychosis. The incidence of elevated serum enzymes during pimovanserin treatment is low, but it has not been found to be associated with clinically significant cases of acute liver injury. See also: pimovasselin tartrate (in salt form).

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Drug Indications
Pimovasselin is indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.
Treatment of schizophrenia and other psychotic disorders.Mechanism of Action
Parkinson's disease psychosis (PDP) is caused by an imbalance of serotonin and dopamine due to disruption of the normal balance between serotonergic and dopaminergic receptors and neurotransmitters in the brain. The mechanism by which pimovasselin treats hallucinations and delusions associated with Parkinson's disease psychosis is not fully understood. Pimovasselin may exert its effects through inverse agonist and antagonist activity on serotonin 5-HT_2A receptors, with limited effects on serotonin 5-HT_2C receptors.
Pemovanserine is an inverse agonist and antagonist of the 5-HT2A receptor, exhibiting high affinity for it but low affinity for the 5-HT2C receptor. Furthermore, it also has low affinity for the σ1 receptor. Pemovanserine is inactive against muscarinic receptors, dopamine receptors, adrenaline receptors, and histamine receptors, thus avoiding the various adverse reactions commonly associated with antipsychotic drugs. Pharmacodynamics: Pemovanserine's unique action on 5-HT receptors can improve hallucinations and delusions associated with Parkinson's disease. Clinical studies have shown that 80.5% of patients treated with pimovasenserine reported symptom improvement. Pemovanserine does not worsen motor dysfunction in patients with Parkinson's disease-related psychosis. In vitro experiments showed that pimovaserin has a high affinity for the 5-HT2A receptor (Ki value 0.087 nM) and a low affinity for the 5-HT2C receptor (Ki value 0.44 nM), acting as both an inverse agonist and an inverse antagonist. Pimovaserin has a low binding affinity for the σ1 receptor (Ki value 120 nM) and no significant affinity for the 5-HT2B receptor, dopaminergic receptors (including D2 receptors), muscarinic receptors, histamine receptors, adrenergic receptors, or calcium channels (Ki value >300 nM). A randomized, placebo-controlled, double-blind, multi-dose parallel, comprehensive QTc study enrolled 252 healthy subjects to evaluate the effect of pimovanzerin on the QTc interval. Central tendency analysis of steady-state QTc data showed that at twice the therapeutic dose, the maximum mean change in QTc interval from baseline (upper limit of the two-sided 90% confidence interval) was 13.5 (16.6) ms. Pharmacokinetic/pharmacodynamic analysis of pimovanzerin suggested a concentration-dependent prolongation of the QTc interval within the therapeutic concentration range. In a 6-week placebo-controlled efficacy study, patients taking 34 mg pimovanzerin once daily experienced a mean QTc interval prolongation of approximately 5–8 ms. These data are consistent with findings observed in comprehensive QT studies in healthy subjects. Occasional QTcF values ≥500 ms and changes from baseline ≥60 ms were observed in subjects receiving 34 mg pimovanzerin; although the overall incidence was similar in the pimovanzerin and placebo groups. In the pimozantine study, no torsades de pointes ventricular tachycardia was reported, and no difference was found in the incidence of other adverse events associated with delayed ventricular repolarization compared to the placebo group, including hallucinations and delusions associated with Parkinson's disease psychosis.

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1. Pimofanserine (ACP-103) is a novel, highly selective 5-HT₂A receptor inverse agonist developed by Acadia Pharmaceuticals for the treatment of neuropsychiatric and motor disorders[1][2]
2. Pimofanserine exerts its pharmacological effect by acting as an inverse agonist of the 5-HT₂A receptor, reducing the constituent activity of the receptor and blocking 5-HT-mediated activation; this mechanism avoids the blocking of dopamine D₂ receptors, thereby eliminating the risk of extrapyramidal side effects associated with typical antipsychotic drugs[1]
3. Pimofanserine was the first drug approved by the FDA for the treatment of Parkinson's disease psychosis (PDP) (2016), and has also shown efficacy in reducing essential tremor and levodopa-induced motor disorders in preclinical models[2]
4. Unlike traditional antipsychotic drugs, pimovaserine does not impair motor function in Parkinson's disease models, making it an effective treatment for Parkinson's disease-related neuropsychiatric symptoms without exacerbating motor disorders [2].

C25H34FN3O2

427.56

427.263

C, 70.23; H, 8.02; F, 4.44; N, 9.83; O, 7.48

706779-91-1

Pimavanserin hemitartrate; 706782-28-7

10071196

White to off-white solid powder

1.1±0.1 g/cm3

604.2±55.0 °C at 760 mmHg

117-119

319.2±31.5 °C

0.0±1.7 mmHg at 25°C

1.576

4.67

1

4

8

31

523

0

CC(C)COC1=CC=C(CNC(N(CC2=CC=C(F)C=C2)C3CCN(C)CC3)=O)C=C1

RKEWSXXUOLRFBX-UHFFFAOYSA-N

InChI=1S/C25H34FN3O2/c1-19(2)18-31-24-10-6-20(7-11-24)16-27-25(30)29(23-12-14-28(3)15-13-23)17-21-4-8-22(26)9-5-21/h4-11,19,23H,12-18H2,1-3H3,(H,27,30)

1-[(4-fluorophenyl)methyl]-1-(1-methylpiperidin-4-yl)-3-[[4-(2-methylpropoxy)phenyl]methyl]urea

ACP-103; BVF-036; ACP 103; BVF036; ACP103; Trade name: Nuplazid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.85 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (5.85 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)