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Dopamine (D2/3) receptor agonist positron emission tomography radiotracer [11C]-(+)-PHNO is a D3 receptor preferring agonist in vivo.
Synapse. 2006 Dec 01; 60(7):485-95.S

Abstract

[11C]PHNO is a recently introduced agonist to image DA D2-like receptors with Positron Emission Tomography (PET). In cats and humans, [11C]PHNO revealed an atypical distribution compared to radiolabeled D2-like antagonists (such as [11C]raclopride) or other D2-like agonists (such as [11C]NPA), as it displayed unusual high binding in the globus pallidus (GP). The goal of this study was to assess the pharmacological nature of the binding of [11C]PHNO in the GP in nonhuman primates. As previously reported in humans, [11C]PHNO equilibrium specific to nonspecific equilibrium partition coefficients (V3'') in baboons was much higher in GP (3.88 +/- 1.15) than in the dorsal striatum (DST, 2.07 +/- 0.43), whereas the reverse was true for [11C]raclopride (1.48 +/- 0.41 in GP, 2.56 +/- 0.91 in DST) and [11C]NPA (0.87 +/- 0.19 in GP, 1.02 +/- 0.13 in DST). Administration of unlabeled raclopride resulted in similar reductions of [11C] PHNO V3'' and [11C]raclopride V3'' in both the GP and the DST. This observation demonstrated that the [11C]PHNO binding in the GP was specific to D2-like receptors. To evaluate the respective contribution of D3 and D2 receptors to the binding potential (BP) of [11C]PHNO and [11C]raclopride, experiments were carried out with the selective D3 partial agonist 1-(4(2-Napthoylamino)butyl)-4-(2-methoxyphenyl)-1A-piperazine HCL (BP897). BP897 reduced [11C]raclopride V3'' by 29% +/- 9%, 19% +/- 8%, and 10% +/- 7% in GP, VST, and DST, respectively, a result consistent with expectation from postmortem studies (D3/D2 ratio in GP > VST > DST). BP897 reduced [11C]PHNO V3'' by 57% +/- 11%, 30% +/- 11%, and 13% +/- 8% in GP, VST, and DST, respectively, indicating that the D3 receptor contribution to [11C]PHNO signal is higher than that of [11C]raclopride. From these experiments we conclude that [11C]PHNO is a D3 preferring agonist, and that this property explains the high GP signal not observed with [11C]raclopride or [11C]NPA. This property might contribute to its higher vulnerability to endogenous DA compared to [11C]raclopride and [11C]NPA.

Authors+Show Affiliations

Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York 10032, USA. narendranr@upmc.eduNo 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)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16952157

Citation

Narendran, Rajesh, et al. "Dopamine (D2/3) Receptor Agonist Positron Emission Tomography Radiotracer [11C]-(+)-PHNO Is a D3 Receptor Preferring Agonist in Vivo." Synapse (New York, N.Y.), vol. 60, no. 7, 2006, pp. 485-95.
Narendran R, Slifstein M, Guillin O, et al. Dopamine (D2/3) receptor agonist positron emission tomography radiotracer [11C]-(+)-PHNO is a D3 receptor preferring agonist in vivo. Synapse. 2006;60(7):485-95.
Narendran, R., Slifstein, M., Guillin, O., Hwang, Y., Hwang, D. R., Scher, E., Reeder, S., Rabiner, E., & Laruelle, M. (2006). Dopamine (D2/3) receptor agonist positron emission tomography radiotracer [11C]-(+)-PHNO is a D3 receptor preferring agonist in vivo. Synapse (New York, N.Y.), 60(7), 485-95.
Narendran R, et al. Dopamine (D2/3) Receptor Agonist Positron Emission Tomography Radiotracer [11C]-(+)-PHNO Is a D3 Receptor Preferring Agonist in Vivo. Synapse. 2006 Dec 1;60(7):485-95. PubMed PMID: 16952157.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopamine (D2/3) receptor agonist positron emission tomography radiotracer [11C]-(+)-PHNO is a D3 receptor preferring agonist in vivo. AU - Narendran,Rajesh, AU - Slifstein,Mark, AU - Guillin,Olivier, AU - Hwang,Yuying, AU - Hwang,Dah-Ren, AU - Scher,Erica, AU - Reeder,Stephanie, AU - Rabiner,Eugenii, AU - Laruelle,Marc, PY - 2006/9/5/pubmed PY - 2006/12/9/medline PY - 2006/9/5/entrez SP - 485 EP - 95 JF - Synapse (New York, N.Y.) JO - Synapse VL - 60 IS - 7 N2 - [11C]PHNO is a recently introduced agonist to image DA D2-like receptors with Positron Emission Tomography (PET). In cats and humans, [11C]PHNO revealed an atypical distribution compared to radiolabeled D2-like antagonists (such as [11C]raclopride) or other D2-like agonists (such as [11C]NPA), as it displayed unusual high binding in the globus pallidus (GP). The goal of this study was to assess the pharmacological nature of the binding of [11C]PHNO in the GP in nonhuman primates. As previously reported in humans, [11C]PHNO equilibrium specific to nonspecific equilibrium partition coefficients (V3'') in baboons was much higher in GP (3.88 +/- 1.15) than in the dorsal striatum (DST, 2.07 +/- 0.43), whereas the reverse was true for [11C]raclopride (1.48 +/- 0.41 in GP, 2.56 +/- 0.91 in DST) and [11C]NPA (0.87 +/- 0.19 in GP, 1.02 +/- 0.13 in DST). Administration of unlabeled raclopride resulted in similar reductions of [11C] PHNO V3'' and [11C]raclopride V3'' in both the GP and the DST. This observation demonstrated that the [11C]PHNO binding in the GP was specific to D2-like receptors. To evaluate the respective contribution of D3 and D2 receptors to the binding potential (BP) of [11C]PHNO and [11C]raclopride, experiments were carried out with the selective D3 partial agonist 1-(4(2-Napthoylamino)butyl)-4-(2-methoxyphenyl)-1A-piperazine HCL (BP897). BP897 reduced [11C]raclopride V3'' by 29% +/- 9%, 19% +/- 8%, and 10% +/- 7% in GP, VST, and DST, respectively, a result consistent with expectation from postmortem studies (D3/D2 ratio in GP > VST > DST). BP897 reduced [11C]PHNO V3'' by 57% +/- 11%, 30% +/- 11%, and 13% +/- 8% in GP, VST, and DST, respectively, indicating that the D3 receptor contribution to [11C]PHNO signal is higher than that of [11C]raclopride. From these experiments we conclude that [11C]PHNO is a D3 preferring agonist, and that this property explains the high GP signal not observed with [11C]raclopride or [11C]NPA. This property might contribute to its higher vulnerability to endogenous DA compared to [11C]raclopride and [11C]NPA. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/16952157/Dopamine__D2/3__receptor_agonist_positron_emission_tomography_radiotracer_[11C]__+__PHNO_is_a_D3_receptor_preferring_agonist_in_vivo_ L2 - https://doi.org/10.1002/syn.20325 DB - PRIME DP - Unbound Medicine ER -