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Pharmacodynamics

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Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents

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Abstract

Over the past 10–15 years, there have been significant advances in our understanding of the pharmacodynamics of neuropsychopharmacological agents. Novel research techniques have allowed for the discovery of multiple receptor subtypes and have also revealed complex and ofttimes seemingly contradictory physiological effects secondary to manipulation of neural receptors. This chapter summarizes key concepts in central nervous system pharmacodynamics including brief descriptions of localization of receptor subtypes, neural pathways, as well as putative pharmacodynamic properties of drugs that affect these neural systems. The aim is to provide clinicians with an understanding of general concepts that may be applied to the relevant chapters in this book and to the literature. This chapter is arranged according to individual neural systems, yet it should be stressed that this “splitting” approach is an artificial attempt to describe, in simple terms, systems that have varying degrees of complex and hitherto not fully understood interrelationships. Indeed, any of the neural systems discussed herein merit their own chapter, if not their own book. It is for this reason that the reader should consult other chapters in this textbook, as well as relevant references for additional details in this complex and quickly evolving field.

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References

  1. Tamminga CA (2002) Partial dopamine agonists in the treatment of psychosis. J Neural Transm 109(3):411–420

    Article  CAS  PubMed  Google Scholar 

  2. Grunder G, Kungel M, Ebrecht M, Gorocs T, Modell S (2006) Aripiprazole: pharmacodynamics of a dopamine partial agonist for the treatment of schizophrenia. Pharmacopsychiatry 39(Suppl 1):S21–S25

    Article  PubMed  CAS  Google Scholar 

  3. Jones BL, Kearns GL (2011) Histamine: new thoughts about a familiar mediator. Clin Pharmacol Ther 89(2):189–197

    Article  CAS  PubMed  Google Scholar 

  4. Simons FE (2004) Advances in H1-antihistamines. N Engl J Med 351(21):2203–2217

    Article  CAS  PubMed  Google Scholar 

  5. Schmith VD, Foss JF (2008) Effects of inflammation on pharmacokinetics/pharmacodynamics: increasing recognition of its contribution to variability in response. Clin Pharmacol Ther 83(6):809–811

    Article  CAS  PubMed  Google Scholar 

  6. Wilkinson GR (2005) Drug metabolism and variability among patients in drug response. N Engl J Med 352(21):2211–2221

    Article  CAS  PubMed  Google Scholar 

  7. Benarroch EE (2012) Blood-brain barrier: recent developments and clinical correlations. Neurology 78(16):1268–1276

    Article  PubMed  Google Scholar 

  8. Zeevi N, Pachter J, McCullough LD, Wolfson L, Kuchel GA (2010) The blood-brain barrier: geriatric relevance of a critical brain-body interface. J Am Geriatr Soc 58(9):1749–1757

    Article  PubMed  PubMed Central  Google Scholar 

  9. Jacobs BL, Azmitia EC (1992) Structure and function of the brain serotonin system. Physiol Rev 72(1):165–229

    CAS  PubMed  Google Scholar 

  10. Adell A, Celada P, Abellan MT, Artigas F (2002) Origin and functional role of the extracellular serotonin in the midbrain raphe nuclei. Brain Res Brain Res Rev 39(2–3):154–180

    Article  CAS  PubMed  Google Scholar 

  11. Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function. Neuropharmacology 38(8):1083–1152

    Article  CAS  PubMed  Google Scholar 

  12. Oleskevich S, Descarries L (1990) Quantified distribution of the serotonin innervation in adult rat hippocampus. Neuroscience 34(1):19–33

    Article  CAS  PubMed  Google Scholar 

  13. Smythies J (2005) Section V, serotonin system. Int Rev Neurobiol 64:217–268

    Article  PubMed  Google Scholar 

  14. Di Matteo V, Cacchio M, Di Giulio C, Esposito E (2002) Role of serotonin (2C) receptors in the control of brain dopaminergic function. Pharmacol Biochem Behav 71(4):727–734

    Article  PubMed  Google Scholar 

  15. Navailles S, De Deurwaerdere P (2011) Presynaptic control of serotonin on striatal dopamine function. Psychopharmacology (Berl) 213(2–3):213–242

    Article  CAS  Google Scholar 

  16. Artigas F (2013) Serotonin receptors involved in antidepressant effects. Pharmacol Ther 137(1):119–131

    Article  CAS  PubMed  Google Scholar 

  17. Millan MJ (2006) Multi-target strategies for the improved treatment of depressive states: conceptual foundations and neuronal substrates, drug discovery and therapeutic application. Pharmacol Ther 110(2):135–370

    Article  CAS  PubMed  Google Scholar 

  18. Celada P, Puig M, Amargos-Bosch M, Adell A, Artigas F (2004) The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J Psychiatry Neurosci 29(4):252–265

    PubMed  PubMed Central  Google Scholar 

  19. Morrissette DA, Stahl SM (2014) Modulating the serotonin system in the treatment of major depressive disorder. CNS Spectr 19(Suppl 1):57–67; Quiz 54–57, 68

    PubMed  Google Scholar 

  20. Yamada M, Yasuhara H (2004) Clinical pharmacology of MAO inhibitors: safety and future. Neurotoxicology 25(1–2):215–221

    Article  CAS  PubMed  Google Scholar 

  21. Carr GV, Lucki I (2011) The role of serotonin receptor subtypes in treating depression: a review of animal studies. Psychopharmacology (Berl) 213(2–3):265–287

    Article  CAS  Google Scholar 

  22. Ramirez MJ, Lai MK, Tordera RM, Francis PT (2014) Serotonergic therapies for cognitive symptoms in Alzheimer’s disease: rationale and current status. Drugs 74(7):729–736

    Article  CAS  PubMed  Google Scholar 

  23. Beaudet A, Descarries L (1978) The monoamine innervation of rat cerebral cortex: synaptic and nonsynaptic axon terminals. Neuroscience 3(10):851–860

    Article  CAS  PubMed  Google Scholar 

  24. Blier P, de Montigny C (1987) Modification of 5-HT neuron properties by sustained administration of the 5-HT1A agonist gepirone: electrophysiological studies in the rat brain. Synapse 1(5):470–480

    Article  CAS  PubMed  Google Scholar 

  25. Innis RB, Aghajanian GK (1987) Pertussis toxin blocks autoreceptor-mediated inhibition of dopaminergic neurons in rat substantia nigra. Brain Res 411(1):139–143

    Article  CAS  PubMed  Google Scholar 

  26. Sprouse JS, Aghajanian GK (1987) Electrophysiological responses of serotoninergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse 1(1):3–9

    Article  CAS  PubMed  Google Scholar 

  27. Neff CD, Abkevich V, Packer JC et al (2009) Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression. Mol Psychiatry 14(6):621–630

    Article  CAS  PubMed  Google Scholar 

  28. Stockmeier CA, Shapiro LA, Dilley GE, Kolli TN, Friedman L, Rajkowska G (1998) Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J Neurosci 18(18):7394–7401

    CAS  PubMed  Google Scholar 

  29. Lemonde S, Turecki G, Bakish D et al (2003) Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci 23(25):8788–8799

    CAS  PubMed  Google Scholar 

  30. Blier P, de Montigny C (1998) Possible serotonergic mechanisms underlying the antidepressant and anti-obsessive-compulsive disorder responses. Biol Psychiatry 44(5):313–323

    Article  CAS  PubMed  Google Scholar 

  31. Blier P, Pineyro G, el Mansari M, Bergeron R, de Montigny C (1998) Role of somatodendritic 5-HT autoreceptors in modulating 5-HT neurotransmission. Ann N Y Acad Sci 861:204–216

    Article  CAS  PubMed  Google Scholar 

  32. Haddjeri N, Blier P, de Montigny C (1998) Long-term antidepressant treatments result in a tonic activation of forebrain 5-HT1A receptors. J Neurosci 18(23):10150–10156

    CAS  PubMed  Google Scholar 

  33. Pineyro G, Blier P, Dennis T, de Montigny C (1994) Desensitization of the neuronal 5-HT carrier following its long-term blockade. J Neurosci 14(5 Pt 2):3036–3047

    CAS  PubMed  Google Scholar 

  34. Deardorff WJ, Grossberg GT (2014) A review of the clinical efficacy, safety and tolerability of the antidepressants vilazodone, levomilnacipran and vortioxetine. Expert Opin Pharmacother 15(17):2525–2542

    Article  CAS  PubMed  Google Scholar 

  35. Garnock-Jones KP (2014) Vortioxetine: a review of its use in major depressive disorder. CNS Drugs 28(9):855–874

    Article  CAS  PubMed  Google Scholar 

  36. de Almeida J, Mengod G (2008) Serotonin 1A receptors in human and monkey prefrontal cortex are mainly expressed in pyramidal neurons and in a GABAergic interneuron subpopulation: implications for schizophrenia and its treatment. J Neurochem 107(2):488–496

    Article  PubMed  CAS  Google Scholar 

  37. Diaz-Mataix L, Scorza MC, Bortolozzi A, Toth M, Celada P, Artigas F (2005) Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action. J Neurosci 25(47):10831–10843

    Article  CAS  PubMed  Google Scholar 

  38. Hajos-Korcsok E, Sharp T (1996) 8-OH-DPAT-induced release of hippocampal noradrenaline in vivo: evidence for a role of both 5-HT1A and dopamine D1 receptors. Eur J Pharmacol 314(3):285–291

    Article  CAS  PubMed  Google Scholar 

  39. Cryan JF, Valentino RJ, Lucki I (2005) Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neurosci Biobehav Rev 29(4–5):547–569

    Article  CAS  PubMed  Google Scholar 

  40. Martin P, Beninger RJ, Hamon M, Puech AJ (1990) Antidepressant-like action of 8-OH-DPAT, a 5-HT1A agonist, in the learned helplessness paradigm: evidence for a postsynaptic mechanism. Behav Brain Res 38(2):135–144

    Article  CAS  PubMed  Google Scholar 

  41. Celada P, Bortolozzi A, Artigas F (2013) Serotonin 5-HT1A receptors as targets for agents to treat psychiatric disorders: rationale and current status of research. CNS Drugs 27(9):703–716

    Article  CAS  PubMed  Google Scholar 

  42. Ballanger B, Strafella AP, van Eimeren T et al (2010) Serotonin 2A receptors and visual hallucinations in Parkinson disease. Arch Neurol 67(4):416–421

    Article  PubMed  Google Scholar 

  43. Huot P, Johnston TH, Darr T et al (2010) Increased 5-HT2A receptors in the temporal cortex of Parkinsonian patients with visual hallucinations. Mov Disord 25(10):1399–1408

    Article  PubMed  Google Scholar 

  44. Ibarretxe-Bilbao N, Junque C, Marti MJ, Tolosa E (2011) Cerebral basis of visual hallucinations in Parkinson’s disease: structural and functional MRI studies. J Neurol Sci 310(1–2):79–81

    Article  PubMed  Google Scholar 

  45. Cummings J, Isaacson S, Mills R et al (2014) Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet 383(9916):533–540

    Article  CAS  PubMed  Google Scholar 

  46. Meltzer HY, Mills R, Revell S et al (2010) Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of Parkinson’s disease psychosis. Neuropsychopharmacology 35(4):881–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Pierre JM (2005) Extrapyramidal symptoms with atypical antipsychotics: incidence, prevention and management. Drug Saf 28(3):191–208

    Article  CAS  PubMed  Google Scholar 

  48. Gillman PK (2011) CNS toxicity involving methylene blue: the exemplar for understanding and predicting drug interactions that precipitate serotonin toxicity. J Psychopharmacol 25(3):429–436

    Article  CAS  PubMed  Google Scholar 

  49. Isbister GK, Buckley NA (2005) The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol 28(5):205–214

    Article  CAS  PubMed  Google Scholar 

  50. Meltzer HY, Roth BL (2013) Lorcaserin and pimavanserin: emerging selectivity of serotonin receptor subtype-targeted drugs. J Clin Invest 123(12):4986–4991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zhang JY, Kowal DM, Nawoschik SP, Lou Z, Dunlop J (2006) Distinct functional profiles of aripiprazole and olanzapine at RNA edited human 5-HT2C receptor isoforms. Biochem Pharmacol 71(4):521–529

    Article  CAS  PubMed  Google Scholar 

  52. Gunes A, Melkersson KI, Scordo MG, Dahl ML (2009) Association between HTR2C and HTR2A polymorphisms and metabolic abnormalities in patients treated with olanzapine or clozapine. J Clin Psychopharmacol 29(1):65–68

    Article  CAS  PubMed  Google Scholar 

  53. Roerig JL, Steffen KJ, Mitchell JE (2011) Atypical antipsychotic-induced weight gain: insights into mechanisms of action. CNS Drugs 25(12):1035–1059

    Article  CAS  PubMed  Google Scholar 

  54. Alex KD, Pehek EA (2007) Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol Ther 113(2):296–320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Aapro M (2005) 5-HT(3)-receptor antagonists in the management of nausea and vomiting in cancer and cancer treatment. Oncology 69(2):97–109

    Article  CAS  PubMed  Google Scholar 

  56. Machu TK (2011) Therapeutics of 5-HT3 receptor antagonists: current uses and future directions. Pharmacol Ther 130(3):338–347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Roth BL, Willins DL, Kristiansen K, Kroeze WK (1998) 5-Hydroxytryptamine2-family receptors (5-hydroxytryptamine2A, 5-hydroxytryptamine2B, 5-hydroxytryptamine2C): where structure meets function. Pharmacol Ther 79(3):231–257

    Article  CAS  PubMed  Google Scholar 

  58. Tfelt-Hansen P, De Vries P, Saxena PR (2000) Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs 60(6):1259–1287

    Article  CAS  PubMed  Google Scholar 

  59. Loder E (2010) Triptan therapy in migraine. N Engl J Med 363(1):63–70

    Article  CAS  PubMed  Google Scholar 

  60. Williams SM, Goldman-Rakic PS (1998) Widespread origin of the primate mesofrontal dopamine system. Cereb Cortex 8(4):321–345

    Article  CAS  PubMed  Google Scholar 

  61. El Mansari M, Guiard BP, Chernoloz O, Ghanbari R, Katz N, Blier P (2010) Relevance of norepinephrine-dopamine interactions in the treatment of major depressive disorder. CNS Neurosci Ther 16(3):e1–e17

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Hamon M, Blier P (2013) Monoamine neurocircuitry in depression and strategies for new treatments. Prog Neuropsychopharmacol Biol Psychiatry 45:54–63

    Article  CAS  PubMed  Google Scholar 

  63. Iversen SD, Iversen LL (2007) Dopamine: 50 years in perspective. Trends Neurosci 30(5):188–193

    Article  CAS  PubMed  Google Scholar 

  64. Dunlop BW, Nemeroff CB (2007) The role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry 64(3):327–337

    Article  CAS  PubMed  Google Scholar 

  65. Sulzer D, Sonders MS, Poulsen NW, Galli A (2005) Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol 75(6):406–433

    Article  CAS  PubMed  Google Scholar 

  66. Gillman PK (2007) Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol 151(6):737–748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Blier P, Gobbi G, Turcotte JE et al (2009) Mirtazapine and paroxetine in major depression: a comparison of monotherapy versus their combination from treatment initiation. Eur Neuropsychopharmacol 19(7):457–465

    Article  CAS  PubMed  Google Scholar 

  68. Blier P, Ward HE, Tremblay P, Laberge L, Hebert C, Bergeron R (2010) Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. Am J Psychiatry 167(3):281–288

    Article  PubMed  Google Scholar 

  69. Watson CJ, Baghdoyan HA, Lydic R (2010) Neuropharmacology of sleep and wakefulness. Sleep Med Clin 5(4):513–528

    Article  PubMed  PubMed Central  Google Scholar 

  70. Watson CJ, Baghdoyan HA, Lydic R (2012) Neuropharmacology of sleep and wakefulness: 2012 update. Sleep Med Clin 7(3):469–486

    Article  PubMed  PubMed Central  Google Scholar 

  71. Miller LJ (2008) Prazosin for the treatment of posttraumatic stress disorder sleep disturbances. Pharmacotherapy 28(5):656–666

    Article  CAS  PubMed  Google Scholar 

  72. Rudolph U, Knoflach F (2011) Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes. Nat Rev Drug Discov 10(9):685–697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Tyson JA, Anderson SA (2014) GABAergic interneuron transplants to study development and treat disease. Trends Neurosci 37(3):169–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Olsen RW, Sieghart W (2009) GABA A receptors: subtypes provide diversity of function and pharmacology. Neuropharmacology 56(1):141–148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Whiting PJ (2003) The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel 6(5):648–657

    CAS  PubMed  Google Scholar 

  76. Blednov YA, Jung S, Alva H et al (2003) Deletion of the alpha1 or beta2 subunit of GABAA receptors reduces actions of alcohol and other drugs. J Pharmacol Exp Ther 304(1):30–36

    Article  CAS  PubMed  Google Scholar 

  77. Reynolds DS, Rosahl TW, Cirone J et al (2003) Sedation and anesthesia mediated by distinct GABA(A) receptor isoforms. J Neurosci 23(24):8608–8617

    CAS  PubMed  Google Scholar 

  78. Morin AK, Jarvis CI, Lynch AM (2007) Therapeutic options for sleep-maintenance and sleep-onset insomnia. Pharmacotherapy 27(1):89–110

    Article  CAS  PubMed  Google Scholar 

  79. Brevig HN, Watson CJ, Lydic R, Baghdoyan HA (2010) Hypocretin and GABA interact in the pontine reticular formation to increase wakefulness. Sleep 33(10):1285–1293

    PubMed  PubMed Central  Google Scholar 

  80. Watson CJ, Soto-Calderon H, Lydic R, Baghdoyan HA (2008) Pontine reticular formation (PnO) administration of hypocretin-1 increases PnO GABA levels and wakefulness. Sleep 31(4):453–464

    PubMed  PubMed Central  Google Scholar 

  81. Bleich S, Romer K, Wiltfang J, Kornhuber J (2003) Glutamate and the glutamate receptor system: a target for drug action. Int J Geriatr Psychiatry 18(Suppl 1):S33–S40

    Article  PubMed  Google Scholar 

  82. Chen HS, Lipton SA (2006) The chemical biology of clinically tolerated NMDA receptor antagonists. J Neurochem 97(6):1611–1626

    Article  CAS  PubMed  Google Scholar 

  83. Benarroch EE (2011) NMDA receptors: recent insights and clinical correlations. Neurology 76(20):1750–1757

    Article  PubMed  Google Scholar 

  84. Zorumski CF, Izumi Y (2012) NMDA receptors and metaplasticity: mechanisms and possible roles in neuropsychiatric disorders. Neurosci Biobehav Rev 36(3):989–1000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44(1):5–21

    Article  CAS  PubMed  Google Scholar 

  86. Wang H, Stradtman GG 3rd, Wang XJ, Gao WJ (2008) A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex. Proc Natl Acad Sci U S A 105(43):16791–16796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Zarate CA, Manji HK (2008) Riluzole in psychiatry: a systematic review of the literature. Expert Opin Drug Metab Toxicol 4(9):1223–1234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Mathew SJ, Manji HK, Charney DS (2008) Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology 33(9):2080–2092

    Article  CAS  PubMed  Google Scholar 

  89. McKeage K (2009) Memantine: a review of its use in moderate to severe Alzheimer’s disease. CNS Drugs 23(10):881–897

    Article  CAS  PubMed  Google Scholar 

  90. Chohan MO, Iqbal K (2006) From tau to toxicity: emerging roles of NMDA receptor in Alzheimer’s disease. J Alzheimers Dis 10(1):81–87

    CAS  PubMed  Google Scholar 

  91. Francis PT, Parsons CG, Jones RW (2012) Rationale for combining glutamatergic and cholinergic approaches in the symptomatic treatment of Alzheimer’s disease. Expert Rev Neurother 12(11):1351–1365

    Article  CAS  PubMed  Google Scholar 

  92. Fox C, Crugel M, Maidment I et al (2012) Efficacy of memantine for agitation in Alzheimer’s dementia: a randomised double-blind placebo controlled trial. PLoS One 7(5):e35185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Maidment ID, Fox CG, Boustani M, Rodriguez J, Brown RC, Katona CL (2008) Efficacy of memantine on behavioral and psychological symptoms related to dementia: a systematic meta-analysis. Ann Pharmacother 42(1):32–38

    Article  PubMed  Google Scholar 

  94. Baronio D, Gonchoroski T, Castro K, Zanatta G, Gottfried C, Riesgo R (2014) Histaminergic system in brain disorders: lessons from the translational approach and future perspectives. Ann Gen Psychiatry 13(1):34. doi:10.1186/s12991-014-0034-y, eCollection 2014

    Article  PubMed  PubMed Central  Google Scholar 

  95. Shan L, Bao AM, Swaab DF (2015) The human histaminergic system in neuropsychiatric disorders. Trends Neurosci 38(3):167–177

    Article  CAS  PubMed  Google Scholar 

  96. Tashiro M, Mochizuki H, Iwabuchi K et al (2002) Roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine H1 receptors in human brain. Life Sci 72(4–5):409–414

    Article  CAS  PubMed  Google Scholar 

  97. Ellenbroek BA, Ghiabi B (2014) The other side of the histamine H3 receptor. Trends Neurosci 37(4):191–199

    Article  CAS  PubMed  Google Scholar 

  98. Haas HL, Sergeeva OA, Selbach O (2008) Histamine in the nervous system. Physiol Rev 88(3):1183–1241

    Article  CAS  PubMed  Google Scholar 

  99. Rojas-Fernandez CH, Chen Y (2014) Use of ultra-low-dose (</=6 mg) doxepin for treatment of insomnia in older people. Can Pharm J (Ott) 147(5):281–289

    Article  Google Scholar 

  100. Mieda M, Sakurai T (2013) Orexin (hypocretin) receptor agonists and antagonists for treatment of sleep disorders. Rationale for development and current status. CNS Drugs 27(2):83–90

    Article  CAS  PubMed  Google Scholar 

  101. He M, Deng C, Huang XF (2013) The role of hypothalamic H1 receptor antagonism in antipsychotic-induced weight gain. CNS Drugs 27(6):423–434

    Article  CAS  PubMed  Google Scholar 

  102. Deng C, Weston-Green K, Huang XF (2010) The role of histaminergic H1 and H3 receptors in food intake: a mechanism for atypical antipsychotic-induced weight gain? Prog Neuropsychopharmacol Biol Psychiatry 34(1):1–4

    Article  PubMed  CAS  Google Scholar 

  103. Cuello AC, Sofroniew MV (1984) The anatomy of the CNS cholinergic neurons. Trends Neurosci 7(3):74–78

    Article  CAS  Google Scholar 

  104. Wenk GL (1997) The nucleus basalis magnocellularis cholinergic system: one hundred years of progress. Neurobiol Learn Mem 67(2):85–95

    Article  CAS  PubMed  Google Scholar 

  105. Benarroch EE (2012) Effects of acetylcholine in the striatum. Recent insights and therapeutic implications. Neurology 79(3):274–281

    Article  CAS  PubMed  Google Scholar 

  106. Benarroch EE (2013) Pedunculopontine nucleus: functional organization and clinical implications. Neurology 80(12):1148–1155

    Article  PubMed  Google Scholar 

  107. Hurst R, Rollema H, Bertrand D (2013) Nicotinic acetylcholine receptors: from basic science to therapeutics. Pharmacol Ther 137(1):22–54

    Article  CAS  PubMed  Google Scholar 

  108. Jimenez-Ruiz C, Berlin I, Hering T (2009) Varenicline: a novel pharmacotherapy for smoking cessation. Drugs 69(10):1319–1338

    Article  CAS  PubMed  Google Scholar 

  109. Benarroch EE (2012) Endogenous opioid systems: current concepts and clinical correlations. Neurology 79(8):807–814

    Article  PubMed  Google Scholar 

  110. Lutz PE, Kieffer BL (2013) Opioid receptors: distinct roles in mood disorders. Trends Neurosci 36(3):195–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Hutcheson JD, Setola V, Roth BL, Merryman WD (2011) Serotonin receptors and heart valve disease – it was meant 2B. Pharmacol Ther 132(2):146–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. DuBeau CE (2009) Therapeutic/pharmacologic approaches to urinary incontinence in older adults. Clin Pharmacol Ther 85(1):98–102

    Article  CAS  PubMed  Google Scholar 

  113. Wagg AS (2012) Antimuscarinic treatment in overactive bladder: special considerations in elderly patients. Drugs Aging 29(7):539–548

    Article  CAS  PubMed  Google Scholar 

  114. Hasselmo ME, Sarter M (2011) Modes and models of forebrain cholinergic neuromodulation of cognition. Neuropsychopharmacology 36(1):52–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Sarter M, Paolone G (2011) Deficits in attentional control: cholinergic mechanisms and circuitry-based treatment approaches. Behav Neurosci 125(6):825–835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Pizzagalli DA (2011) Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology 36(1):183–206

    Article  PubMed  PubMed Central  Google Scholar 

  117. Carlson PJ, Diazgranados N, Nugent AC et al (2013) Neural correlates of rapid antidepressant response to ketamine in treatment-resistant unipolar depression: a preliminary positron emission tomography study. Biol Psychiatry 73(12):1213–1221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Nugent AC, Diazgranados N, Carlson PJ et al (2014) Neural correlates of rapid antidepressant response to ketamine in bipolar disorder. Bipolar Disord 16(2):119–128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Schlegel Research Chair, Geriatric Pharmacotherapy Schlegel-UW Research Institute for Ageing, Waterloo, ON, Canada

    Carlos H. Rojas-Fernandez BSc(Pharm), PharmD (President)

  2. CRF Consulting Services, Geriatric Clinical Pharmacology, Neuropsychopharmacology, Clinical & Epidemiologic Research, Waterloo, ON, Canada

    Carlos H. Rojas-Fernandez BSc(Pharm), PharmD (President)

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  1. Carlos H. Rojas-Fernandez BSc(Pharm), PharmD
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Correspondence to Carlos H. Rojas-Fernandez BSc(Pharm), PharmD .

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Editors and Affiliations

  1. Univ. North Texas Sys, Col Pharmacy, Department of Pharmacotherapy, FORT WORTH, Texas, USA

    Michael W. Jann

  2. Department of Pharmacotherapy, Univ. North Texas Sys, Col Pharm, FORT WORTH, Texas, USA

    Scott R. Penzak

  3. Department of Pharmacotherapy, Univ. North Texas Sys, Col Pharm., FORT WORTH, Texas, USA

    Lawrence J. Cohen

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Rojas-Fernandez, C.H. (2016). Pharmacodynamics. In: Jann, M., Penzak, S., Cohen, L. (eds) Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents. Adis, Cham. https://doi.org/10.1007/978-3-319-27883-4_2

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  • DOI: https://doi.org/10.1007/978-3-319-27883-4_2

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  • Publisher Name: Adis, Cham

  • Print ISBN: 978-3-319-27881-0

  • Online ISBN: 978-3-319-27883-4

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