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Obsessive-Compulsive Disorder: Experimental Pharmacology

Published online by Cambridge University Press:  07 November 2014

Donatella Marazziti
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Abstract

There is evidence supporting the presence of abnormalities in certain neurotransmitters, such as dopamine and noradrenaline, and in neuropeptides and other mechanisms, such as the immune system in patients with obsessive-compulsive disorder (OCD). However, the findings implicating serotonin (5-hydroxytryptamine [5-HT]) in the pathophysiology of OCD are increasing at a rate not found in any other psychiatric disorder. These abundant findings foster numerous complex questions that await answers. For example, which 5-HT receptor subtypes or other subcomponents of the 5-HT system are principally involved in OCD pathophysiology, and how do they interact with dysfunctions of other systems? In the search for answers to these critical questions, experimental pharmacology represents a key tool for approaching the complexity of the involvement of 5-HT in OCD, and also suggests new potential therapeutic targets. This article summarizes, in part, the presentations and the discussion of the symposium, “Experimental Pharmacology in OCD,” which was held during the Third International OCD Conference meeting in Madeira, Portugal, in September 1998.

Type
Academic Supplement Monograph
Information
CNS Spectrums , Volume 4 , supplement S3: The Third International Obsessive-Compulsive Disorder Conference , May 1999 , pp. 41 - 45
Copyright
Copyright © Cambridge University Press 1999

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References

REFERENCES

1.Montgomery, SA. Pharmacological treatment of obsessive-compulsive disorder. In: Hollander, E, Zohar, J, Marazziti, D, Olivier, B, eds. Current Insights in Obsessive-Compulsive Disorder. Chichester, UK: Wiley & Sons; 1994:215–226.Google Scholar
2.Piccinelli, M, Pini, S, Bellantuono, C, Wilkinson, C. Efficacy of drug treatment in obsessive-compulsive disorder. Br J Psychiatry. 1995;166:424–443.CrossRefGoogle ScholarPubMed
3.Greist, JH, Jefferson, JW, Kobak, KH, Katzenlick, DJ, Serlin, RC. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. Arch Gen Psychiatry. 1995;52:53–60.CrossRefGoogle ScholarPubMed
4.Fineberg, N. Refining treatment approaches in obsessive-compulsive disorder. J Clin Psychopharmacol. 1996;11(suppl 5):13–22.CrossRefGoogle ScholarPubMed
5.Insel, TR, Mueller, EA, Alterman, I, Linnoila, M, Murphy, DL. Obsessive-compulsive disorder and serotonin: is there a connection? Biol Psychiatry. 1985;20:1174–1188.CrossRefGoogle ScholarPubMed
6.Thoren, P, Asberg, M, Cronholm, B. Clomipramine treatment of obsessive-compulsive disorder: a controlled clinical trial. Arch Gen Psychiatry. 1980;37:1281–1289.CrossRefGoogle ScholarPubMed
7.Asberg, M, Thoren, P, Bertilsson, L. Chlomipramine treatment of obsessive disorder: biochemical and clinical aspects. Psychopharmacol Bull. 1981;18:13–21.Google Scholar
8.Zohar, J, Insel, TR. Obsessive-compulsive disorder: psychobiological approaches to diagnosis, treatment and pathophysiology. Biol Psychiatry. 1987;22:667–687.CrossRefGoogle ScholarPubMed
9.Hollander, E, Fay, M, Cohen, B, Campeas, R, Gorman, JM, Liebowitz, MR. Serotonergic and noradrenergic sensitivity in obsessive-compulsive disorder: behavioral findings. Arch Gen Psychiatry. 1988;145:1015–1023.Google ScholarPubMed
10.Zohar, J, Insel, TR, Zohar-Kadouch, RC, Hill, J, Murphy, DL. Serotonergic responsivity in obsessive-compulsive disorder: effect of chronic clomipramine treatment. Arch Gen Psychiatry. 1988;45:167–172.CrossRefGoogle ScholarPubMed
11.Lesch, KP, Wolozin, BL, Murphy, DL, Riederer, P. Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem. 1993;60:2319–2322.CrossRefGoogle ScholarPubMed
12.Rausch, JJ, Hutchinson, J, Li, X. Correlations of drug action between human platelets and human brain 5HTT. Biol Psychiatry. 1995;137(suppl):600.CrossRefGoogle Scholar
13.Meyerson, LR, Ieni, JR, Wennogle, LP. Allosteric interaction between the site labelled by H-imipramine and the serotonin transporter in human platelets. J Neurochem. 1987;48:560–565.CrossRefGoogle Scholar
14.Hrdina, PD. Differences between sodium-dependent and desipramine-defined H-imipramine binding in intact human platelets. Biol Psychiatry. 1989;25:576–584.CrossRefGoogle Scholar
15.Marcusson, JO, Fowler, CJ, Hall, H, Ross, SB, Winblad, B. “Specific” binding of 3H-imipramine to protease-sensitive and protease-resistant sites. J Neurochem. 1985;44:705–711.CrossRefGoogle Scholar
16.Weizman, R, Carmi, M, Hermesh, H, et al.High-affinity imipramine binding and serotonin uptake in platelets of eight adolescent and ten adult obsessive-compulsive patients. Am J Psychiatry. 1986;143:335–339.Google ScholarPubMed
17.Marazziti, D, Hollander, E, Lensi, P, Ravagli, S, Cassano, GB. Peripheral marker of serotonin and dopamine function in obsessive-compulsive disorder. Psychiatry Res. 1992;42:41–51.CrossRefGoogle ScholarPubMed
18.Black, DW, Kelly, M, Myers, C, Noyes, R Jr.Tritiated imipramine binding in obsessive-compulsive volunteers and psychiatrically normal controls. Biol Psychiatry. 1990;27:319–327.CrossRefGoogle ScholarPubMed
19.Bastani, B, Arora, RC, Meltzer, HY. Serotonin uptake and imipramine binding in the blood platelets of obsessive-compulsive disorder patients. Biol Psychiatry. 1991;30:131–139.CrossRefGoogle ScholarPubMed
20.Vitiello, B, Shimon, H, Behar, D, Stoff, D, Bridger, WH, Friedman, E. Platelet imipramine binding and serotonin uptake in obsessive-compulsive patients. Acta Psychiatr Scand. 1991;84:29–32.CrossRefGoogle ScholarPubMed
21.Mann, CD, Hrdina, PPD. Sodium dependence of 3H-paroxetine binding and 5- H-hydroxytryptamine uptake in rat diencephalon. J Neurochem. 1992;59:1856–1861.CrossRefGoogle Scholar
22.Mellerup, ET, Plenge, P, Engelstoft, M. High-affinity binding of 3H-paroxetine and 3H-imipramine to human platelet membranes. Eur J Pharmacol. 1983;96:303–309.CrossRefGoogle Scholar
23.Marazziti, D, Rossi, A, Gemignani, A, et al.Decreased platelet H-paroxetine binding in obsessive-compulsive patients. Neuropsychobiology. 1996;34:184–187.CrossRefGoogle Scholar
24.Sallee, FR, Richman, H, Beach, K, Sethuram, G, Nesbitt, L. Platelet serotonin transporter in children and adolescents with obsessive-compulsive disorder or Tourette's syndrome. J Am Acad Child Adolesc Psychiatry. 1996;35:1647–1656.CrossRefGoogle ScholarPubMed
25.Hollander, E, DeCaria, C, Wong, CM, Aronowitz, B. Predictors of SSRI treatment response in OCD and autism. 1998:191. CINP Abstracts.Google Scholar
26.Zohar, Y, Sasson, Y, Chopra, M, Groos, R. Predictors of response in OCD. 1998:191.CINP Abstracts.Google Scholar
27.Marazziti, D. Predictors of response. Eur Neuropsychopharmacol. 1997;27(suppl 2):101–102.CrossRefGoogle Scholar
28.Hoyer, D, Martin, G. 5-HT receptor classification and nomenclature: towards a harmonization with the human genome. Neuropharmacology. 1997;36:419–428.CrossRefGoogle ScholarPubMed
29.Blier, P, De Montigny, C. Possible serotonergic mechanisms underlying the antidepressant and anti-obsessive-compulsive disorder responses. Biol Psychiatry. 1998;44:312–323.CrossRefGoogle ScholarPubMed
30.Benkefalt, , Murphy, DL, Zohar, J, Hill, JL, Grover, G, Insel, TR. Clomipramine in obsessive-compulsive disorder: further evidence for a serotonergic mechanism of action. Arch Gen Psychiatry. 1989;46:23–28.Google Scholar
31.Erzegovesi, S, Ronchi, P, Smeraldi, E. 5-HT2 receptor and fluvoxamine in obsessive-compulsive disorder. Human Psychopharmacology. 1992;7:287–289.CrossRefGoogle Scholar
32.Moreno, FA, Delgado, PL. Hallucinogen-induced relief of obsessions and compulsions. Am J Psychiatry. 1997;145:1037–1038.Google Scholar
33.McDougle, CJ. Update on pharmacologic management of OCD: agents and augmentation. J Clin Psychiatry. 1997;58(suppl 12):11–17.Google ScholarPubMed
34.Pigott, TA, Zohar, J, Hill, JL, et al.Metergoline blocks the behavioral and neuroendocrine effects of orally administered m-chlorophenylpiperazine in patients with obsessive-compulsive disorder. Biol Psychiatry. 1991;29:418–426.CrossRefGoogle ScholarPubMed
35.Bastani, B, Nash, F, Meltzer, H. Prolactin and cortisol response to MK-212, a serotonin agonist, in obsessive-compulsive disorder. Arch Gen Psychiatry. 1990;47:946–951.CrossRefGoogle ScholarPubMed
36.Stern, L, Zohar, J, Hendler, T, Ianco, I, Sasson, Y. The potential role of 5-HT1D receptors in the pathophysiology of obsessive-compulsive disorder. CNS Spectrums. 1998;3(8):46–49.CrossRefGoogle Scholar
37.Ho Pian, KL, Westenberg, HGM, van Megen, HJGM, Den Boer, JA. Sumatriptan (5-HT1D receptor agonist) does not exacerbate symptoms in obsessive-compulsive disorder. Psychopharmacology. In press.Google Scholar
38.Lesch, KP, Hoh, A, Disselkamp-Tietze, J, et al.5-hydroxytryptaminelA receptor activity in obsessive-compulsive disorder: comparison of patients and controls. Arch Gen Psychiatry. 1991;48:540–547.CrossRefGoogle Scholar
39.McDougle, CJ, Goodman, WK, Leckman, JF, et al.Limited therapeutic efficacy of addition of buspirone in fluvoxamine-refractory obsessive-compulsive disorder. Am J Psychiatry. 1993;150:647–649.Google Scholar
40.Broock, A, Pigott, TA, Hill, JL, et al.Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive-compulsive disorder (OCD): behavioral and biological results. Psychiatry Res. 1998;79:11–20.CrossRefGoogle Scholar
41.Anderson, GM, Horne, WC. Activators of protein kinase C decrease serotonin transport in human platelets. Biochem Biophys Acta. 1992;1137:331–337.Google Scholar
42.De Vivo, M, Maayani, S. Inhibition of forskolin stimulation adenylate cyclase activity by 5-HT receptor agonist. Eur J Pharmacol. 1985;119(3):231–234.CrossRefGoogle Scholar
43.Nishizuka, Y. Studies and perspective of protein kinase C. Science. 1986;233:305–312.CrossRefGoogle ScholarPubMed
44.Kikkawa, U, Kishimoto, A, Nishizuka. The protein kinase C family: heterogeneity and its implications. Annu Rev Biochem. 1989;58:31–44.CrossRefGoogle ScholarPubMed
45.Wilkinson, SE, Hallam, TJ. Protein kinase C: is its pivotal role in cellular activation over-stated? Trends Pharmacol Sci. 1994;15:53–57.CrossRefGoogle ScholarPubMed
46.Berridge, MJ, Downes, CP, Hanley, MR. Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J. 1982;206:587–595.CrossRefGoogle ScholarPubMed
47.Ashendel, CL. The phorbol ester receptor: a phospholipid-regulated protein kinase. Biochem Biophys Acta. 1985;822:219–242.Google ScholarPubMed
48.Weiss, S, Ellis, J, Hendley, DD, Lenox, RH. Translocation and activation of protein kinase C in striatal neurons in primary culture: relationship to phorbol dibutyrate actions on the inositol phosphate generating system and neurotransmitter release. J Neurochem. 1989;52:530–536.CrossRefGoogle ScholarPubMed
49.Marazziti, D, Rossi, A, Masala, I, et al.Regulation of the platelet serotonin transporter by protein kinase C in the young and elderly. Biol Psychiatry. In press.Google Scholar
50.Wang, HY, Friedman, E. Central 5-hydroxytryptamine receptor-linked protein kinase C translocation: a functional postsynaptic signal transduction system. Mol Pharmacol. 1990;37:75–79.Google ScholarPubMed
51.Fux, M, Levine, J, Aviv, A, Belmaker, RH. Inositol treatment of obsessive-compulsive disorder. Am J Psychiatry. 1996;153:1219–1221.Google ScholarPubMed
52.Duman, RS. Novel therapeutic approaches beyond the serotonin receptor. Biol Psychiatry. 1998;44:324–335.CrossRefGoogle ScholarPubMed
53.Greden, JF. Serotonin: how much we have learned! So much to discover. Biol Psychiatry. 1998;44:309–311.Google ScholarPubMed