Skip to main content Accessibility help
×
Home
Hostname: page-component-5cfd469876-tkzrn Total loading time: 0.274 Render date: 2021-06-25T01:37:23.299Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true }

Positron Emission Tomography of in-vivo Binding Characteristics of Atypical Antipsychotic Drugs

Review of D2 and 5-HT2 Receptor Occupancy Studies and Clinical Response

Published online by Cambridge University Press:  06 August 2018

Svante Nyberg
Affiliation:
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden
Yoshifumi Nakashima
Affiliation:
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden
Anna-Lena Nordström
Affiliation:
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden
Christer Halldin
Affiliation:
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden
Lars Farde
Affiliation:
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden

Extract

Several types of neuroreceptors are of interest with respect to antipsychotic activity, in particular the D2, D1, and 5-HT2 receptors. Among currently prescribed antipsychotic drugs, some have an affinity for a broad range of neuroreceptors, while others are more selective for the D2 receptor (Hytell et al, 1985). The most widely accepted hypothesis of neuroleptic drug action is that antipsychotic effects are mediated by a blockade of the dopamine receptors (Carlsson & Lindqvist, 1963; van Rossum, 1966; Creese et al, 1976; Seeman et al, 1976; Peroutka & Snyder, 1980). This hypothesis has been supported by consistent findings of high D2 receptor occupancy in positron emission tomography (PET) studies of patients treated with antipsychotic drugs (Farde et al, 1986; Smith et al, 1988; Baron et al, 1989). At the same time, the risk of extrapyramidal side-effects (EPS) seems particularly high in patients with occupancy above 80% (Farde et al, 1992) (Fig. 1).

Type
Research Article
Copyright
Copyright © 1996 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below.

References

Balsara, J. J., Jadhav, J. H. & Chandorkar, A. G. (1979) Effect of drugs influencing central serotonergic mechanisms on haloperidol-induced catalepsy. Psychopharmacology, 62, 6769.CrossRefGoogle ScholarPubMed
Baron, J. C., Martinot, J. L., Cambon, H., et al (1989) Striatal dopamine receptor occupancy during and following withdrawal from neuroleptic treatment: correlative evaluation by positron emission tomography and plasma prolactin levels. Psychopharmacology, 99, 463472.CrossRefGoogle ScholarPubMed
Bersani, G., Grispini, A., Marini, S., et al (1990) 5-HT2 antagonist ritanserin in neuroleptic-induced parkinsonism: a double-blind comparison with orphenadrine and placebo. Clinical Neuropharmacology, 13, 500506.CrossRefGoogle ScholarPubMed
Carlsson, A. & Lindqvist, M. (1963) Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacologica et Toxicologica, 20, 140144.CrossRefGoogle ScholarPubMed
Ceulemans, D. L. S., Gelders, Y. G., Hoppenbrouwers, M.-L. J. A., et al (1985) Effect of serotonin antagonism in schizophrenia: a pilot study with setoperone. Psychopharmacology, 85, 329332.CrossRefGoogle ScholarPubMed
Claus, A., Bollen, J., De Cuyper, H., et al (1992) Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: a multicentre double-blind comparative study. Acta Psychiatrica Scandinavica, 85, 295305.CrossRefGoogle ScholarPubMed
Costall, B., Fortune, D. H., Naylor, R. J., et al (1975) Serotonergic involvement with neuroleptic catalepsy. Neuropharmacology, 14, 859868.CrossRefGoogle ScholarPubMed
Creese, I., Burt, D. R. & Snyder, S. H. (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science, 192, 481483.CrossRefGoogle ScholarPubMed
Farde, L., Hall, H., Ehrin, E., et al (1986) Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science, 231, 258261.CrossRefGoogle ScholarPubMed
Farde, L., Wiesel, F.-A., Nordström, A.-L., et al (1989a) D1- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology, 99, S28S31.CrossRefGoogle Scholar
Farde, L., Eriksson, L., Blomquist, G., et al (1989b) Kinetic analysis of central [11C]raclopride binding to D2-dopamine receptors studies by PET – a comparison to the equilibrium analysis. Journal of Cerebral Blood Flow Metabolism, 9, 696708.CrossRefGoogle Scholar
Farde, L., Wiesel, F.-A., Stone-Elander, S., et al (1990) D2 dopamine receptors in neuroleptic-naïve schizophrenic patients. Archives of General Psychiatry, 47, 213219.CrossRefGoogle ScholarPubMed
Farde, L., Nordström, A.-L., Wiesel, F.-A., et al (1992) Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to extrapyramidal side effects. Archives of General Psychiatry, 49, 538544.CrossRefGoogle ScholarPubMed
Gelders, Y., Vanden Bussche, G., Reyntjens, A., et al (1986) Serotonin-S2 receptor blockers in the treatment of chronic schizophrenia. Clinical Neuropharmacology, 9 (suppl. 4), S325–S327.Google Scholar
Gerlach, J. (1991) New antipsychotics: classification, efficacy, and adverse effects. Schizophrenia Bulletin, 17, 289309.CrossRefGoogle ScholarPubMed
Halldin, C., Farde, L., Högberg, T., et al (1991) A comparative PET-study of five carbon-11 or fluorine-18 labelled salicylamides. Preparation and in vitro dopamine D2 binding. Nuclear Medicine Biology, 18, 871881.Google ScholarPubMed
Hicks, P. B. (1990) The effect of serotonergic agents on haloperidol-induced catalepsy. Life Sciences, 47, 16091615.CrossRefGoogle ScholarPubMed
Hytell, J., Larsen, J. J., Christensen, A. V., et al (1985) Receptor-binding profiles of neuroleptics. In Dyskinesia: Research and Treatment (eds Casey, D. E., Chase, T. N. & Christensen, A. V.), pp. 918. New York: Springer.CrossRefGoogle Scholar
Kane, J., Honigfeld, G., Singer, J., et al (1988) Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Archives of General Psychiatry, 45, 789796.CrossRefGoogle ScholarPubMed
Korsgaard, S., Gerlach, J. & Christensson, E. (1985) Behavioural aspects of serotonin–dopamine interaction in the monkey. European Journal of Pharmacology, 118, 245252.CrossRefGoogle ScholarPubMed
Kostowski, W., Gumulka, W. & Czlonkowski, A. (1972) Reduced cataleptogenic effects of some neuroleptics in rats with lesioned midbrain raphe and treated with p-chlorophenylalinine. Brain Research, 48, 443446.Google ScholarPubMed
Leysen, J. E., Gommeren, W., Eens, A., et al (1988) Biochemical profile of risperidone, a new antipsychotic. Journal of Pharmacology and Experimental Therapeutics, 247, 661670.Google ScholarPubMed
Lieberman, J. A. (1994) Understanding the mechanism of action of atypical antipsychotic drugs. A review of compounds in use and development. British Journal of Psychiatry, 163 (suppl. 22), 718.Google Scholar
Litton, J., Bergström, K., Eriksson, L., et al (1984) Performance study of the PC-384 positron camera system for emission tomography of the brain. Computer Assisted Tomography, 8, 7487.CrossRefGoogle Scholar
Litton, J., Holte, S. & Eriksson, L. (1990) Evaluation of the Karolinska new positron camera system: the Scanditronix PC2048-156B. IEEE Transmission on Nuclear Science, 37, 743748.CrossRefGoogle Scholar
Marder, S. R. (1992) Risperidone: clinical development: North American results. Clinical Neuropharmacology, 15 (suppl. 1, Pt A), 92A.CrossRefGoogle ScholarPubMed
Marder, S. R. & Meibach, R. C. (1994) Risperidone in the treatment of schizophrenia. American Journal of Psychiatry, 151, 825835.Google ScholarPubMed
Meltzer, H. Y. (1991) The mechanism of action of novel antipsychotic drugs. Schizophrenia Bulletin, 17, 263287.CrossRefGoogle ScholarPubMed
Meltzer, H. Y., Matsubara, S. & Lee, J.-C. (1989) The ratios of serotonin-2 and dopamine-2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacology Bulletin 25, 390392.Google Scholar
Mizuki, Y., Kajamura, N., Imai, T., et al (1990) Effects of mianserin on negative symptoms in schizophrenia. International Journal of Clinical Psychopharmacology, 5, 8395.CrossRefGoogle Scholar
Müller-Spahn, F. (1992) Risperidone in the treatment of chronic schizophrenic patients: an international double-blind parallel-group study versus haloperidol. Clinical Neuropharmacology, 15 (suppl. 1, Pt A), 90A.CrossRefGoogle ScholarPubMed
Nordström, A.-L. (1993) PET Evaluation of Dopamine Hypothesis for Antipsychotic Drugs and Schizophrenia. Department of Psychiatry and Psychology, Karolinska Insitute, Stockholm, Sweden.Google Scholar
Nordström, A.-L., Farde, L., Pauli, S., et al (1992) PET analysis of central [11C]raclopride binding in healthy young adults and schizophrenic patients – reliability and age effects. Human Psychopharmacology, 7, 157165.CrossRefGoogle Scholar
Nordström, A.-L., Farde, L. & Halldin, C. (1993) High 5-HT2 receptor occupancy in clozapine treated patients demonstrated by PET. Psychopharmacology, 110, 365367.CrossRefGoogle ScholarPubMed
Nyberg, S., Farde, L., Eriksson, L., et al (1993) 5-HT2 and D2 dopamine receptor occupancy in the living human brain: a PET study with risperidone. Psychopharmacology, 110, 265272.CrossRefGoogle ScholarPubMed
Peroutka, S. J. & Snyder, S. H. (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, α-adrenergic, and histamine receptors to clinical potency. American Journal of Psychiatry, 137, 15181522.Google ScholarPubMed
Reyntjens, A., Gelders, Y. G., Hoppenbrouwers, M.-L. J. A., et al (1986) Thymosthenic effects of ritanserin (R 55667), a centrally acting serotonin-S2 receptor blocker. Drug Development Research, 8, 205211.CrossRefGoogle Scholar
Seeman, P., Lee, T., Chau-Wong, M., et al (1976) Antipsychotic drug doses and neuroleptic/dopamine receptor. Nature, 261, 717719.CrossRefGoogle Scholar
Silver, H, & Nassar, A. (1992) Fluvoxamine improves negative symptoms in treated chronic schizophrenia: an add-on double-blind, placebo-controlled study. Biological Psychiatry, 31, 698704.CrossRefGoogle ScholarPubMed
Silver, H, Blacker, M., Weller, M. P. I., et al (1989) Treatment of chronic schizophrenia with cyproheptadine. Biological Psychiatry, 25, 502504.CrossRefGoogle ScholarPubMed
Smith, M., Wolf, A. P., Brodie, J. D., et al (1988) Serial [18F]N-methylspiroperidol PET studies to measure changes in antipsychotic drug D-2 receptor occupancy in schizophrenic patients. Biological Psychiatry, 23, 653663.Google ScholarPubMed
Trichard, C., Paillère-Martinot, M. L., Monfort, J. C., et al (1992) Cortical 5-HT2 receptors and antipsychotic drugs studied with PET in schizophrenia: preliminary results. (Proceedings of the AEP sixth European Congress, Barcelona, November 3–7). Anales de Psiquiatria, 8 (suppl. 1), 9.Google Scholar
van Rossum, J. M. (1966) The significance of dopamine receptor blockade for the mechanism of action of neuroleptic drugs. Archives Internationales de Pharmacodynamic et de Thérapie, 160, 492494.Google ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.
53
Cited by

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Positron Emission Tomography of in-vivo Binding Characteristics of Atypical Antipsychotic Drugs
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Positron Emission Tomography of in-vivo Binding Characteristics of Atypical Antipsychotic Drugs
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Positron Emission Tomography of in-vivo Binding Characteristics of Atypical Antipsychotic Drugs
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *