Scientific Publications

NUPLAZID® (also known as pimavanserin or ACP-103)

Cummings J, et al.: Pimavanserin for patients with Parkinson’s disease psychosis: a randomized, placebo-controlled phase 3 trial. The Lancet, 383, 533-540 (2014).
Hacksell U, et al.: On the Discovery and Development of Pimavanserin: A Novel Drug Candidate for Parkinson’s Psychosis. Neurochemistry Research, 39, 2008-2017 (2014).
Ballard C, et al.: Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis. Journal of the American Medical Directors Association, e-pub (2015).
Meltzer HY, et al.: Pimavanserin, a serotonin 2A receptor inverse agonist for the treatment of Parkinson’s disease psychosis. Neuropsychopharmacology, 35, 881-892 (2010).
Ballard C, et al.: Evaluation of the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer’s disease psychosis: a phase 2, randomised, placebo-controlled, double-blind study. The Lancet, 17, 213-22 (2018).
Meltzer HY, et al.: Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2 mg/day, but does not enhance efficacy of haloperidol, 2 mg/day: Comparison with reference dose risperidone, 6 mg/day. Schizophrenia Research, 141, 144-152 (2012).
Ancoli-Israel S., et al.: Pimavanserin tartrate, a 5-HT2A receptor inverse agonist, increases slow wave sleep as measured by polysomnography in healthy adult volunteers. Sleep Medicine, 12, 134-141 (2011).
Nordstrom AL, et al.: PET analysis of the 5-HT2A receptor inverse agonist ACP-103 in human brain. The International Journal of Neuropsychopharmacology, 11, 163-171 (2007).
Vanover KE, et al.: Pharmacokinetics, Tolerability, and Safety of ACP-103 Following Single or Multiple Oral Dose Administration in Healthy Volunteers. The Journal of Clinical Pharmacology, 47, 704-714 (2007).
Vanover KE, et al.: A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model. Pharmacology Biochemistry and Behavior, 90, 540-544 (2008).
McFarland, et al.: Pimavanserin, a 5-HT2A inverse agonist, reverses psychosis-like behaviors in a rodent model of Parkinson’s disease. Behavioural Pharmacology, 22, 681-692 (2011).
Hubbard D, et al.: Behavioral effects of clozapine, pimavanserin, and quetiapine in rodent models of Parkinson’s disease and Parkinson’s disease psychosis: evaluation of therapeutic ratios. Behavioural Pharmacology, 24, 628-632 (2013).
Price DL, et al.: Pimavanserin, a 5-HT2A receptor inverse agonist, reverses psychosis-like behaviors in a rodent model of Alzheimer’s disease. Behavioural Pharmacology, 23, 426-433 (2012).
Gardell LR, et al.: ACP-103, A 5-Hydroxytryptamine 2A Receptor Inverse Agonist, Improves the Antipsychotic Efficacy and Side-Effect Profile of Haloperidol and Risperidone in Experimental Models. The Journal of Pharmacology and Experimental Therapeutics, 322, 862-870 (2007).
Vanover KE, et al.: 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-Hydroxytryptamine2A Receptor Inverse Agonist. The Journal of Pharmacology and Experimental Therapeutics, 317, 910-918 (2006).

Other Relevant Scientific Publications

McFarland K, et al.: Low-Dose Bexarotene Treatment Rescues Dopamine Neurons and Restores Behavioral Function in Models of Parkinson’s Disease. ACS Chemical Neuroscience, 4:1430-1438 (2013).
Ma JN, et al.: The Protease Activated Receptor 2 (PAR2) Polymorphic Variant F240S Constitutively Activates PAR2 Receptors and Potentiates Responses to Small-Molecule PAR2 Agonists. The Journal of Pharmacology and Experimental Therapeutics, 347, 697-704 (2013).
George S, et al.: Nonsteroidal Selective Androgen Receptor Modulators and Selective Estrogen Receptor Beta Agonists Moderate Cognitive Deficits and Amyloid-Beta Levels in a Mouse Model of Alzheimer’s Disease. ACS Chemical Neuroscience, 4:1537-1548 (2013).
Ma JN, et al.: Characterization of highly efficacious allosteric agonists of the human calcium receptor. Journal of Pharmacology and Experimental Therapeutics, 337, 275-284 (2011).
Gaubert G., et al.: Discovery of Selective Nonpeptidergic Neuropeptide FF2 Receptor Agonists. Journal of Medicinal Chemistry, 52, 6511-6514 (2009).
Del Tredici AL, et al.: Identification of novel selective V2 receptor non-peptide agonists. Biochemical Pharmacology, 76, 1134-1141 (2008).
Piu F, et al.: Broad modulation of neuropathic pain states by a selective estrogen receptor beta agonist. European Journal of Pharmacology, 590, 423-429 (2008).
Piu F, et al.: Pharmacological characterization of AC-262536, a novel selective androgen receptor modulator. The Journal of Steroid Biochemistry and Molecular Biology, 109, 129-137 (2008).
Burstein ES, et al.: Integrative Functional Assays, Chemical Genomics and High Throughput Screening: Harnessing Signal Transduction Pathways to a Common HTS Readout. Current Pharmaceutical Design, 12, 1717-1729 (2006).
Weiner DM, et al.: Psychosis of Parkinson’s disease: Serotonin 2A receptor inverse agonists as potential therapeutics. Current Opinion in Investigational Drugs, 4, 815-819 (2003).
Weiner DM, et al.: 5-Hydroxytryptamine2A Receptor Inverse Agonists as Antipsychotics. The Journal of Pharmacology and Experimental Therapeutics, 299, 268-276 (2001).

Trofinetide

Glaze DG, et al.: A double‐blind, randomized, placebo‐controlled clinical study of trofinetide in the treatment of Rett syndrome. Pediatr. Neurol., 76:37-46 (2017).
Neul, et al.: Improving treatment trial outcomes for Rett syndrome: the development of Rett-specific anchors for the Clinical Global Impression Scale. Journal of Child Neurology, 1-6 (2015).
Deacon, et al.: NNZ-2566, a novel analog of (1–3) IGF-1, as a potential therapeutic agent for Fragile X syndrome. Neuromolecular Medicine, 17, 71-82 (2015).
Cartagena, et al.: Mechanism of action for NNZ-2566 anti-inflammatory effects following PBBI involves upregulation of immunomodulator ATF3. NeuroMolecular Medicine, 15 (3), 504-14 (2013).
Lu, et al.: NNZ-2566, a glypromate analog, improves functional recovery and attenuates apoptosis and inflammation in a rat model of penetrating ballistic-type brain injury. Journal of Neurotrauma, 26, 141–154 (2009).
Lu, et al.: NNZ-2566, a glypromate analog, attenuates brain ischemia-induced nonconvulsive seizures in rats. Journal of Cerebral Blood Flow & Metabolism, 00, 1-9 (2009).
Wei, et al.: NNZ-2566, treatment inhibits neuroinflammation and pro-inflammatory cytokine expression induced by experimental penetrating ballistic-like brain injury in rats. Journal of Neuroinflammation, 6, 19-29 (2009).
Bickerdike, et al.: NNZ-2566, A Gly–Pro–Glu analogue with neuroprotective efficacy in a rat model of acute focal stroke. Journal of the Neurological Sciences, 278 (1-2), 85-90 (2009).
Svedin, et al.: Delayed peripheral administration of a GPE analogue induces astrogliosis and angiogenesis and reduces inflammation and brain injury following hypoxia-ischemia in the neonatal rat. Developmental Neuroscience, 29, 393-402 (2007).

Other Relevant Scientific Publications

Derecki, et al.: Microglia as a critical player in both developmental and late-life CNS pathologies. Acta Neuropathologica, 128, 333-345 (2014).
Bozdagi, et al.: IGF-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay. Molecular Autism, 4:9 (2013).
Schafer, et al.: The Quad-partite synapse: microglia-synapse interactions in the developing and mature CNS. Glia, 61, 24-36 (2013).
Suh, et al.: IGF-1 and IGF-2 expression in human microglia differential regulation by inflammatory mediators. Journal of Neuroinflammation, 10:37 (2013).
Corvin, et al.: IGF1 and its active peptide (1–3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms. Neuroscience Letters, 520, 51-56 (2012).
De Filippis, et al.: Modulation of RhoGTPases Improves the Behavioral Phenotype and Reverses Astrocytic Deficits in a Mouse Model of Rett Syndrome. Neuropsychopharmacology, 37, 1152-1163 (2012).
Derecki, et al.: Wild type microglia arrest pathology in a mouse model of Rett syndrome. Nature, 484 (7392), 105-109 (2012).
Lioy, et al.: A role for glia in the progression of Rett syndrome. Nature, 475 (7357), 497-500 (2011).
Maezawa, et al.: Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. Journal of Neuorscience, 30 (15), 5346-5356 (2010).
Gonzales, et al.: The role of MeCP2 in brain development and neurodevelopmental disorders. Current Psychiatric Reports, 12, 127-134 (2010).
Tropea, et al.: Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. PNAS, 106, 2029-2034 (2009).
Luikenhuis, et al.: Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. PNAS, 101, 6033-6038 (2004).
Smeets, et al.: Rett syndrome in adolescent and adult females: clinical and molecular genetic findings. American Journal of Medical Genetics, 122A, 227-233 (2003).
Shahbazian, et al.: Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron, 35, 243-254 (2002).
Sizonenko, et al.: Neuroprotective effects of the N-terminal tripeptide of IGF-1, glycine-proline-glutamate, in the immature rat brain after hypoxic–ischemic injury. Brain Research, 922, 42-50 (2001).
Saura, et al.: Neuroprotective effects of Gly-Pro-Glu, the Nterminal tripeptide of IGF-1, in the hippocampus in vitro. NeuroReport, 10, 161-164 (1999).
Amir, et al.: Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genetics, 23, 183-188 (1999).
Beck, et al.: IGF-1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatial parvalbumin-containing neurons. Neuron, 14, 717-730 (1995).