793
Views
27
CrossRef citations to date
0
Altmetric
Review

Phosphodiesterase 10 inhibitors in clinical development for CNS disorders

, &
Pages 553-560 | Received 22 Jul 2016, Accepted 01 Dec 2016, Published online: 10 Dec 2016

References

  • Hyman SE. Time for new schizophrenia Rx. Science. 2014;343(6176):1177.
  • Keefe RS, Meltzer HA, Dgetluck N, et al. Randomized, double-blind, placebo-controlled study of encenicline, an alpha7 nicotinic acetylcholine receptor agonist, as a treatment for cognitive impairment in schizophrenia. Neuropsychopharmacology. 2015;40(13):3053–3060.
  • Duinen MV, Reneerkens OA, Lambrecht L, et al. treatment of cognitive impairment in schizophrenia: potential value of phosphodiesterase inhibitors in prefrontal dysfunction. Curr Pharm Des. 2015;21(26):3813–3828.
  • Pacheco-Cano MT, Bargas J, Hernandez-Lopez S, et al. Inhibitory action of dopamine involves a subthreshold cs(+)-sensitive conductance in neostriatal neurons. Exp Brain Res. 1996;110(2):205–211.
  • Surmeier DJ, Bargas J, Hemmings HC Jr., et al. Modulation of calcium currents by a D1 dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons. Neuron. 1995;14(2):385–397.
  • Hernandez-Lopez S, Bargas J, Surmeier DJ, et al. D1 receptor activation enhances evoked discharge in neostriatal medium spiny neurons by modulating an L-type Ca2+ conductance. J Neurosci. 1997;17(9):3334–3342.
  • Tseng KY, Snyder-Keller A, O’Donnell P. Dopaminergic modulation of striatal plateau depolarizations in corticostriatal organotypic cocultures. Psychopharmacology. 2007;191(3):627–640.
  • Nishi A, Kuroiwa M, Miller DB, et al. Distinct roles of PDE4 and PDE10A in the regulation of cAMP/PKA signaling in the striatum. J Neuroscience. 2008;28(42):10460–10471.
  • Perez MF, White FJ, Hu XT. Dopamine D(2) receptor modulation of K(+) channel activity regulates excitability of nucleus accumbens neurons at different membrane potentials. J Neurophysiol. 2006;96(5):2217–2228.
  • Greengard P. The neurobiology of slow synaptic transmission. Science. 2001;294(5544):1024–1030.
  • Qi Z, Miller GW, Voit EO. The internal state of medium spiny neurons varies in response to different input signals. BMC Syst Biol. 2010;4:26.
  • Padovan-Neto FE, Sammut S, Chakroborty S, et al. Facilitation of corticostriatal transmission following pharmacological inhibition of striatal phosphodiesterase 10A: role of nitric oxide-soluble guanylyl cyclase-cGMP signaling pathways. J Neurosci. 2015;35(14):5781–5791.
  • Calabresi P, Gubellini P, Centonze D, et al. A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression. J Neuroscience. 1999;19(7):2489–2499.
  • Picconi B, Bagetta V, Ghiglieri V, et al. Inhibition of phosphodiesterases rescues striatal long-term depression and reduces levodopa-induced dyskinesia. Brain. 2011;134(Pt 2):375–387.
  • Wilson LS, Brandon NJ. Emerging biology of PDE10A. Curr Pharm Des. 2015;21(3):378–388.
  • Kehler J, Nielsen J. PDE10A inhibitors: novel therapeutic drugs for schizophrenia. Curr Pharm Des. 2011;17(2):137–150.
  • Peuskens J, Pani L, Detraux J, et al. The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review. CNS Drugs. 2014;28(5):421–453.
  • Boswell-Smith V, Spina D, Page CP. Phosphodiesterase inhibitors. Br J Pharmacol. 2006;147(Suppl 1):S252–257.
  • Schmidt CJ, Chapin DS, Cianfrogna J, et al. Preclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia. J Pharmacol Exp Ther. 2008;325(2):681–690.
  • Jones PG, Hewitt MC, Campbell JE, et al. Pharmacological evaluation of a novel phosphodiesterase 10A inhibitor in models of antipsychotic activity and cognition. Pharmacol Biochem Behav. 2015;135:46–52.
  • Suzuki K, Harada A, Shiraishi E, et al. In vivo pharmacological characterization of TAK-063, a potent and selective phosphodiesterase 10A inhibitor with antipsychotic-like activity in rodents. J Pharmacol Exp Ther. 2015;352(3):471–479.
  • Bartolome-Nebreda JM, Delgado F, Martin-Martin ML, et al. Discovery of a potent, selective, and orally active phosphodiesterase 10A inhibitor for the potential treatment of schizophrenia. J Med Chem. 2014;57(10):4196–4212.
  • Megens AAHP, Hendrickx HMR, Hens KA, et al. Pharmacology of JNJ-42314415, a centrally active phosphodiesterase 10A (PDE10A) inhibitor: a comparison of PDE10A inhibitors with D2 receptor blockers as potential antipsychotic drugs. J Pharmacol Exp Ther. 2014;349(1):138–154.
  • Hu E, Chen N, Bourbeau MP, et al. Discovery of clinical candidate 1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)e thanone (AMG 579), a potent, selective, and efficacious inhibitor of phosphodiesterase 10A (PDE10A). J Med Chem. 2014;57(15):6632–6641.
  • Smith SM, Uslaner JM, Cox CD, et al. The novel phosphodiesterase 10A inhibitor THPP-1 has antipsychotic-like effects in rat and improves cognition in rat and rhesus monkey. Neuropharmacology. 2013;64:215–223.
  • Gage JL, Onrust R, Johnston D, et al. N-Acylhydrazones as inhibitors of PDE10A. Bioorg Med Chem Lett. 2011;21(14):4155–4159.
  • Suzuki K, Harada A, Suzuki H, et al. Tak-063, a pde10a inhibitor with balanced activation of direct and indirect pathways, provides potent antipsychotic-like effects in multiple paradigms. Neuropsychopharmacology. 2016;41(9):2252–2262.
  • Reneerkens OA, Rutten K, Bollen E, et al. Inhibition of phoshodiesterase type 2 or type 10 reverses object memory deficits induced by scopolamine or MK-801. Behav Brain Res. 2013;236(1):16–22.
  • Nikiforuk A, Potasiewicz A, Rafa D, et al. The effects of PDE10 inhibition on attentional set-shifting do not depend on the activation of dopamine D1 receptors. Behav Pharmacol. 2016;27(4):331–338.
  • Weber M, Breier M, Ko D, et al. Evaluating the antipsychotic profile of the preferential PDE10A inhibitor, papaverine. Psychopharmacology. 2009;203(4):723–735.
  • Nakai S, Hirose T, Mori T, et al. The effect of aripiprazole on prepulse inhibition of the startle response in normal and hyperdopaminergic states in rats. Int J Neurosci. 2008;118(1):39–57.
  • Uthayathas S, Masilamoni GJ, Shaffer CL, et al. Phosphodiesterase 10A inhibitor MP-10 effects in primates: comparison with risperidone and mechanistic implications. Neuropharmacology. 2014;77:257–267.
  • Reneerkens OA, Sambeth A, Blokland A, et al. PDE2 and PDE10, but not PDE5, inhibition affect basic auditory information processing in rats. Behav Brain Res. 2013;250:251–256.
  • Redrobe JP, Rasmussen LK, Christoffersen CT, et al. Characterisation of Lu AF33241: A novel, brain-penetrant, dual inhibitor of phosphodiesterase (PDE) 2A and PDE10A. Eur J Pharmacol. 2015;761:79–85.
  • Li N, Chen X, Zhu B, et al. Suppression of beta-catenin/TCF transcriptional activity and colon tumor cell growth by dual inhibition of PDE5 and 10. Oncotarget. 2015;6(29):27403–27415.
  • Little S, Pogosyan A, Neal S, et al. Adaptive deep brain stimulation in advanced Parkinson disease. Ann Neurol. 2013;74(3):449–457.
  • Garcia AM, Redondo M, Martinez A, et al. 10 inhibitors: new disease modifying drugs for Parkinson’s disease? Curr Med Chem. 2014;21(10):1171–1187.
  • Giampa C, Laurenti D, Anzilotti S, et al. Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington’s disease. Plos ONE. 2010;5(10):e13417.
  • Niccolini F, Foltynie T, Reis Marques T, et al. Loss of phosphodiesterase 10A expression is associated with progression and severity in Parkinson’s disease. Brain. 2015;138(Pt 10):3003–3015.
  • Lewis DA, Pierri JN, Volk DW, et al. Altered GABA neurotransmission and prefrontal cortical dysfunction in schizophrenia. Biol Psychiatry. 1999;46(5):616–626.
  • Choi ML, Begeti F, Oh JH, et al. Dopaminergic manipulations and its effects on neurogenesis and motor function in a transgenic mouse model of Huntington’s disease. Neurobiol Dis. 2014;66:19–27.
  • Giralt A, Saavedra A, Carreton O, et al. PDE10 inhibition increases GluA1 and CREB phosphorylation and improves spatial and recognition memories in a Huntington’s disease mouse model. Hippocampus. 2013;23(8):684–695.
  • Wilson JM, Ogden AM, Loomis S, et al. Phosphodiesterase 10A inhibitor, MP-10 (PF-2545920), produces greater induction of c-Fos in dopamine D2 neurons than in D1 neurons in the neostriatum. Neuropharmacology. 2015;99:379–386.
  • Gruber AJ, Solla SA, Surmeier DJ, et al. Modulation of striatal single units by expected reward: a spiny neuron model displaying dopamine-induced bistability. J Neurophysiol. 2003;90(2):1095–1114.
  • Kruse LS, Moller M, Tibaek M, et al. PDE9A, PDE10A, and PDE11A expression in rat trigeminovascular pain signalling system. Brain Res. 2009;1281:25–34.
  • Mu Y, Ren Z, Jia J, et al. Inhibition of phosphodiesterase10A attenuates morphine-induced conditioned place preference. Mol Brain. 2014;7:70.
  • Logrip ML, Vendruscolo LF, Schlosburg JE, et al. Phosphodiesterase 10A regulates alcohol and saccharin self-administration in rats. Neuropsychopharmacology. 2014;39(7):1722–1731.
  • Chen H, Lester-Zeiner D, Shi J, et al. AMG 580: a novel small molecule phosphodiesterase 10A (PDE10A) positron emission tomography tracer. J Pharmacol Exp Ther. 2015;352(2):327–337.
  • Harada A, Suzuki K, Miura S, et al. Characterization of the binding properties of T-773 as a PET radioligand for phosphodiesterase 10A. Nucl Med Biol. 2015;42(2):146–154.
  • Takano A, Stepanov V, Gulyas B, et al. Evaluation of a novel PDE10A PET radioligand, [(11) C]T-773, in nonhuman primates: brain and whole body PET and brain autoradiography. Synapse. 2015;69(7):345–355.
  • Toth M, Haggkvist J, Stepanov V, et al. molecular imaging of pde10a knockout mice with a novel pet radiotracer: [(11)C]T-773. Mol Imaging Biol. 2015;17(4):445–449.
  • Takano A, Stepanov V, Nakao R, et al. Brain PET measurement of PDE10A occupancy by TAK-063, a new PDE10A inhibitor, using [C]T-773 in nonhuman primates. Synapse. 2016;141:10–17.
  • Lin SF, Labaree D, Chen MK, et al. Further evaluation of [11C]MP-10 as a radiotracer for phosphodiesterase 10A: PET imaging study in rhesus monkeys and brain tissue metabolite analysis. Synapse. 2015;69(2):86–95.
  • Kehler J, Kilburn JP, Estrada S, et al. Discovery and development of 11C-Lu AE92686 as a radioligand for PET imaging of phosphodiesterase10A in the brain. J Nucl Med. 2014;55(9):1513–1518.
  • Barret O, Thomae D, Tavares A, et al. In vivo assessment and dosimetry of 2 novel PDE10A PET radiotracers in humans: 18F-MNI-659 and 18F-MNI-654. J Nucl Med. 2014;55(8):1297–1304.
  • Hwang DR, Hu E, Rumfelt S, et al. Initial characterization of a PDE10A selective positron emission tomography tracer [11C]AMG 7980 in non-human primates. Nucl Med Biol. 2014;41(4):343–349.
  • Hostetler ED, Fan H, Joshi AD, et al. Preclinical Characterization of the Phosphodiesterase 10A PET Tracer [C]MK-8193. Mol Imaging Biol. 2016;18(4):579–587.
  • Cox CD, Hostetler ED, Flores BA, et al. Discovery of [(11)C]MK-8193 as a PET tracer to measure target engagement of phosphodiesterase 10A (PDE10A) inhibitors. Bioorg Med Chem Lett. 2015;25(21):4893–4898.
  • Liu H, Jin H, Yue X, et al. Preclinical evaluation of a promising C-11 labeled PET tracer for imaging phosphodiesterase 10A in the brain of living subject. NeuroImage. 2015;121:253–262.
  • Li YW, SeagerMA, Wojcik T et al. Biochemical and behavioral effects of PDE10A inhibitors: Relationship to target site occupancy. Neuropharmacology, 102, 121–135 (2016).
  • Niccolini F, Foltynie T, Reis Marques T, et al. Loss of phosphodiesterase 10A expression is associated with progression and severity in Parkinson’s disease. Brain. 2015;138(Pt 10):3003–3015.
  • Marques TR, Natesan S, Niccolini F, et al. Phosphodiesterase 10A in Schizophrenia: A PET Study Using [C]IMA107. Am J Psychiatry. 2016. appiajp201515040518.
  • Niccolini F, Haider S, Reis Marques T, et al. Altered PDE10A expression detectable early before symptomatic onset in Huntington’s disease. Brain. 2015;138(Pt 10):3016–3029.
  • Natesan S, Reckless GE, Barlow KB, et al. The antipsychotic potential of l-stepholidine–a naturally occurring dopamine receptor D1 agonist and D2 antagonist. Psychopharmacology. 2008;199(2):275–289.
  • Yue K, Ma B, Chen L, et al. L-Stepholidine, a naturally occurring dopamine D1 receptor agonist and D2 receptor antagonist, attenuates heroin self-administration and cue-induced reinstatement in rats. NeuroReport. 2014;25(1):7–11.
  • Mo J, Zhang H, Yu LP, et al. L-stepholidine reduced L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson’s disease. Neurobiol Aging. 2010;31(6):926–936.
  • Hao JR, Sun N, Lei L, et al. L-Stepholidine rescues memory deficit and synaptic plasticity in models of Alzheimer’s disease via activating dopamine D1 receptor/PKA signaling pathway. Cell Death Dis. 2015;6:e1965.
  • Rosell DR, Zaluda LC, McClure M M, et al. Effects of the D1 dopamine receptor agonist dihydrexidine (DAR-0100A) on working memory in schizotypal personality disorder. Neuropsychopharmacology. 2015;40(2):446–453.
  • Niccolini F, Haider S, Reis Marques T, et al. Altered PDE10A expression detectable early before symptomatic onset in Huntington’s disease. Brain. 2015;138(Pt 10):3016–3029.
  • Ahmad R, Bourgeois S, Postnov A, et al. PET imaging shows loss of striatal PDE10A in patients with Huntington disease. Neurology. 2014;82(3):279–281.
  • Abi-Dargham A, Rodenhiser J, Printz D, et al. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci U S A. 2000;97(14):8104–8109.
  • Patel VD, Lee DE, Alexoff DL, et al. Imaging dopamine release with Positron Emission Tomography (PET) and (11)C-raclopride in freely moving animals. NeuroImage. 2008;41(3):1051–1066.
  • Spiros A, Carr R, Geerts H. Not all partial dopamine D(2) receptor agonists are the same in treating schizophrenia. Exploring the effects of bifeprunox and aripiprazole using a computer model of a primate striatal dopaminergic synapse. Neuropsychiatr Dis Treat. 2010;6:589–603.
  • Meyer-Lindenberg A, Miletich RS, Kohn PD, et al. Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Nat Neurosci. 2002;5(3):267–271.
  • Coyle JT. Glutamate and schizophrenia: beyond the dopamine hypothesis. Cell Mol Neurobiol. 2006;26(4–6):365–384.
  • Winterer G, Ziller M, Dorn H, et al. Schizophrenia: reduced signal-to-noise ratio and impaired phase-locking during information processing. Clin Neurophysiol. 2000;111(5):837–849.
  • Modinos G, Allen P, Grace AA, et al. Translating the MAM model of psychosis to humans. Trends Neurosci. 2015;38(3):129–138.
  • Geerts H. Of mice and men: bridging the translational disconnect in CNS drug discovery. CNS Drugs. 2009;23(11):915–926.
  • Kapur S. Antipsychotic dosing in preclinical models is often unrepresentative of the clinical condition: a suggested solution based on in vivo occupancy. J Pharmacol Exp Ther. 2003;305(2):625–631.
  • Gill KM, Cook JM, Poe MM, et al. Prior antipsychotic drug treatment prevents response to novel antipsychotic agent in the methylazoxymethanol acetate model of schizophrenia. Schizophr Bull. 2014;40(2):341–350.
  • Bamford NS, Robinson S, Palmiter RD, et al. Dopamine modulates release from corticostriatal terminals. J Neurosci. 2004;24(43):9541–9552.
  • Swapna I, Bondy B, Morikawa H. Differential dopamine regulation of ca(2+) signaling and its timing dependence in the nucleus accumbens. Cell Rep. 2016;15(3):563–573.
  • Geerts H, Kennis L. Multitarget drug discovery projects in CNS diseases: quantitative systems pharmacology as a possible path forward. Future Med Chem. 2014;6(16):1757–1769.
  • Lenz JD, Lobo MK. Optogenetic insights into striatal function and behavior. Behav Brain Res. 2013;255:44–54.
  • Farrell MS, Pei Y, Wan Y, et al. A Galphas DREADD mouse for selective modulation of cAMP production in striatopallidal neurons. Neuropsychopharmacology. 2013;38(5):854–862.
  • Xie YZ, Zhang RX. Neurodegenerative diseases in a dish: the promise of iPSC technology in disease modeling and therapeutic discovery. Neurological Sciences. 2015;36(1):21–27.
  • Roberts P, Spiros A, Geerts H. A Humanized clinically calibrated quantitative systems pharmacology model for hypokinetic motor symptoms in Parkinson’s Disease. Front Pharmacol. 2016;7:6.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.