Tags

Type your tag names separated by a space and hit enter

The effect of antipsychotics on the high-affinity state of D2 and D3 receptors: a positron emission tomography study With [11C]-(+)-PHNO.
Arch Gen Psychiatry. 2009 Jun; 66(6):606-15.AG

Abstract

CONTEXT

Most antipsychotics are thought to have an effect on D(2) and D(3) receptors. The development of carbon 11-labeled (+)-4-propyl-9-hydroxynaphthoxazine ([(11)C]-(+)-PHNO), the first agonist radioligand with higher affinity for D(3) than D(2) receptors, allows one to differentiate the effects of antipsychotics on high-affinity vs low-affinity sites of the D(2) receptor and on D(3) vs D(2) receptor subtypes.

OBJECTIVES

To examine the effects of antipsychotics (clozapine, risperidone, or olanzapine) on the high- vs high- + low-affinity sites of the D(2) and D(3) receptors by comparing the [(11)C]-(+)-PHNO and [(11)C]raclopride binding in the D(3) receptor-rich (globus pallidus and ventral striatum) and D(2) receptor-rich (caudate and putamen) regions.

DESIGN

Two sequential studies with different participants and appropriate controls were performed. The first compared the occupancy produced by 3 antipsychotics as measured with [(11)C]-(+)-PHNO and [(11)C]raclopride. The second was a double-blind, placebo-controlled experiment to compare the effect of pramipexole (a D(3) receptor-preferring agonist) vs placebo on the increased [(11)C]-(+)-PHNO signal observed in the globus pallidus of patients.

SETTING

Positron Emission Tomography Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

PARTICIPANTS

Twenty-three patients with schizophrenia and 23 healthy controls.

MAIN OUTCOME MEASURES

Antipsychotic occupancies as measured with [(11)C]-(+)-PHNO and [(11)C]raclopride.

RESULTS

The antipsychotic-treated patients showed high occupancies with both [(11)C]-(+)-PHNO and [(11)C]raclopride in the dorsal striatum, with [(11)C]raclopride occupancies about 20% higher. Most strikingly, patients did not show any occupancy with [(11)C]-(+)-PHNO in the globus pallidus as compared with normal controls or with their own scans using [(11)C]raclopride. This unblocked [(11)C]-(+)-PHNO signal was displaced by a single dose of pramipexole.

CONCLUSIONS

Antipsychotics block both the high- and low-affinity states of the D(2) receptors across the brain, but antipsychotic treatment does not block the [(11)C]-(+)-PHNO signal in the D(3) receptor-rich regions, despite the ongoing D(2) receptor blockade. This [(11)C]-(+)-PHNO signal in regions such as the globus pallidus seems increased despite antipsychotic treatment and is displaceable by a D(3) receptor-preferring agonist. The radiotracer [(11)C]-(+)-PHNO and the data open up new avenues for exploring the potential therapeutic significance of the D(3) receptor in schizophrenia.

Authors+Show Affiliations

PO Box 053, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, England.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Controlled Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19487625

Citation

Graff-Guerrero, Ariel, et al. "The Effect of Antipsychotics On the High-affinity State of D2 and D3 Receptors: a Positron Emission Tomography Study With [11C]-(+)-PHNO." Archives of General Psychiatry, vol. 66, no. 6, 2009, pp. 606-15.
Graff-Guerrero A, Mamo D, Shammi CM, et al. The effect of antipsychotics on the high-affinity state of D2 and D3 receptors: a positron emission tomography study With [11C]-(+)-PHNO. Arch Gen Psychiatry. 2009;66(6):606-15.
Graff-Guerrero, A., Mamo, D., Shammi, C. M., Mizrahi, R., Marcon, H., Barsoum, P., Rusjan, P., Houle, S., Wilson, A. A., & Kapur, S. (2009). The effect of antipsychotics on the high-affinity state of D2 and D3 receptors: a positron emission tomography study With [11C]-(+)-PHNO. Archives of General Psychiatry, 66(6), 606-15. https://doi.org/10.1001/archgenpsychiatry.2009.43
Graff-Guerrero A, et al. The Effect of Antipsychotics On the High-affinity State of D2 and D3 Receptors: a Positron Emission Tomography Study With [11C]-(+)-PHNO. Arch Gen Psychiatry. 2009;66(6):606-15. PubMed PMID: 19487625.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of antipsychotics on the high-affinity state of D2 and D3 receptors: a positron emission tomography study With [11C]-(+)-PHNO. AU - Graff-Guerrero,Ariel, AU - Mamo,David, AU - Shammi,C M, AU - Mizrahi,Romina, AU - Marcon,Heidi, AU - Barsoum,Penny, AU - Rusjan,Pablo, AU - Houle,Sylvain, AU - Wilson,Alan A, AU - Kapur,Shitij, PY - 2009/6/3/entrez PY - 2009/6/3/pubmed PY - 2009/6/10/medline SP - 606 EP - 15 JF - Archives of general psychiatry JO - Arch Gen Psychiatry VL - 66 IS - 6 N2 - CONTEXT: Most antipsychotics are thought to have an effect on D(2) and D(3) receptors. The development of carbon 11-labeled (+)-4-propyl-9-hydroxynaphthoxazine ([(11)C]-(+)-PHNO), the first agonist radioligand with higher affinity for D(3) than D(2) receptors, allows one to differentiate the effects of antipsychotics on high-affinity vs low-affinity sites of the D(2) receptor and on D(3) vs D(2) receptor subtypes. OBJECTIVES: To examine the effects of antipsychotics (clozapine, risperidone, or olanzapine) on the high- vs high- + low-affinity sites of the D(2) and D(3) receptors by comparing the [(11)C]-(+)-PHNO and [(11)C]raclopride binding in the D(3) receptor-rich (globus pallidus and ventral striatum) and D(2) receptor-rich (caudate and putamen) regions. DESIGN: Two sequential studies with different participants and appropriate controls were performed. The first compared the occupancy produced by 3 antipsychotics as measured with [(11)C]-(+)-PHNO and [(11)C]raclopride. The second was a double-blind, placebo-controlled experiment to compare the effect of pramipexole (a D(3) receptor-preferring agonist) vs placebo on the increased [(11)C]-(+)-PHNO signal observed in the globus pallidus of patients. SETTING: Positron Emission Tomography Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. PARTICIPANTS: Twenty-three patients with schizophrenia and 23 healthy controls. MAIN OUTCOME MEASURES: Antipsychotic occupancies as measured with [(11)C]-(+)-PHNO and [(11)C]raclopride. RESULTS: The antipsychotic-treated patients showed high occupancies with both [(11)C]-(+)-PHNO and [(11)C]raclopride in the dorsal striatum, with [(11)C]raclopride occupancies about 20% higher. Most strikingly, patients did not show any occupancy with [(11)C]-(+)-PHNO in the globus pallidus as compared with normal controls or with their own scans using [(11)C]raclopride. This unblocked [(11)C]-(+)-PHNO signal was displaced by a single dose of pramipexole. CONCLUSIONS: Antipsychotics block both the high- and low-affinity states of the D(2) receptors across the brain, but antipsychotic treatment does not block the [(11)C]-(+)-PHNO signal in the D(3) receptor-rich regions, despite the ongoing D(2) receptor blockade. This [(11)C]-(+)-PHNO signal in regions such as the globus pallidus seems increased despite antipsychotic treatment and is displaceable by a D(3) receptor-preferring agonist. The radiotracer [(11)C]-(+)-PHNO and the data open up new avenues for exploring the potential therapeutic significance of the D(3) receptor in schizophrenia. SN - 1538-3636 UR - https://www.unboundmedicine.com/medline/citation/19487625/The_effect_of_antipsychotics_on_the_high_affinity_state_of_D2_and_D3_receptors:_a_positron_emission_tomography_study_With_[11C]__+__PHNO_ L2 - https://jamanetwork.com/journals/jamapsychiatry/fullarticle/10.1001/archgenpsychiatry.2009.43 DB - PRIME DP - Unbound Medicine ER -