Antiparkinson concentrations of pramipexole and PHNO occupy dopamine D2(high) and D3(high) receptors.
Identifieur interne : 001227 ( PubMed/Curation ); précédent : 001226; suivant : 001228Antiparkinson concentrations of pramipexole and PHNO occupy dopamine D2(high) and D3(high) receptors.
Auteurs : Philip Seeman [Canada] ; Françoise Ko ; Matth Us Willeit ; Patrick Mccormick ; Nathalie GinovartSource :
- Synapse (New York, N.Y.) [ 0887-4476 ] ; 2005.
English descriptors
- KwdEn :
- Animals, Benzothiazoles, Binding, Competitive (drug effects), Binding, Competitive (physiology), Brain (drug effects), Brain (metabolism), Cells, Cultured, Cricetinae, Domperidone (metabolism), Dopamine Agonists (metabolism), Dopamine Agonists (pharmacology), Dopamine Antagonists (metabolism), Dose-Response Relationship, Drug, Humans, Mice, Neurons (drug effects), Neurons (metabolism), Oxazines (metabolism), Oxazines (pharmacology), Parkinson Disease (drug therapy), Parkinson Disease (metabolism), Parkinson Disease (physiopathology), Radioligand Assay, Rats, Receptors, Dopamine D2 (drug effects), Receptors, Dopamine D2 (metabolism), Receptors, Dopamine D3 (drug effects), Receptors, Dopamine D3 (metabolism), Synapses (drug effects), Synapses (metabolism), Synaptic Transmission (drug effects), Synaptic Transmission (physiology), Thiazoles (metabolism), Thiazoles (pharmacology), Tritium.
- MESH :
- chemical , drug effects : Receptors, Dopamine D2, Receptors, Dopamine D3.
- chemical , metabolism : Domperidone, Dopamine Agonists, Dopamine Antagonists, Oxazines, Receptors, Dopamine D2, Receptors, Dopamine D3, Thiazoles.
- chemical , pharmacology : Dopamine Agonists, Oxazines, Thiazoles.
- chemical : Benzothiazoles, Tritium.
- drug effects : Binding, Competitive, Brain, Neurons, Synapses, Synaptic Transmission.
- drug therapy : Parkinson Disease.
- metabolism : Brain, Neurons, Parkinson Disease, Synapses.
- physiology : Binding, Competitive, Synaptic Transmission.
- physiopathology : Parkinson Disease.
- Animals, Cells, Cultured, Cricetinae, Dose-Response Relationship, Drug, Humans, Mice, Radioligand Assay, Rats.
Abstract
Because the high-affinity state of dopamine D2 receptors, D2(High), is the functional state of D2, and because the proportion of D2 receptors in the high-affinity state correlates with dopamine behavioral supersensitivity, the present study was designed to determine the affinities of antiparkinson dopamine agonists at the D2(High) site by means of competition with [3H]domperidone. In contrast to [125I]iodosulpride or [3H]spiperone, which are not sensitive to low concentrations of dopamine agonists, [3H]domperidone readily reveals dissociation constants (K(i)) for antiparkinson agonists at D2(High) and D3(High) receptors. The K(i) values for the human cloned D2(High) and D3(High) receptors, respectively, were 19 and 9 nM for pramipexole, 0.24 and 0.6 nM for +PHNO, 0.7 and 1.3 nM for bromocriptine, 0.5 and 2.6 nM for apomorphine, and 0.09 and 0.25 nM for (-)N-propylnorapomorphine. After correcting for the fraction of drug bound to plasma proteins, the known clinical concentrations in plasma or plasma water of these drugs, including pramipexole and +PHNO, are sufficient to occupy and activate the high-affinity state of D2, D2(High), in treating Parkinson's disease. The D3(High) receptors are less selectively occupied by +PHNO, bromocriptine, apomorphine, and -NPA.
DOI: 10.1002/syn.20193
PubMed: 16088951
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In contrast to [125I]iodosulpride or [3H]spiperone, which are not sensitive to low concentrations of dopamine agonists, [3H]domperidone readily reveals dissociation constants (K(i)) for antiparkinson agonists at D2(High) and D3(High) receptors. The K(i) values for the human cloned D2(High) and D3(High) receptors, respectively, were 19 and 9 nM for pramipexole, 0.24 and 0.6 nM for +PHNO, 0.7 and 1.3 nM for bromocriptine, 0.5 and 2.6 nM for apomorphine, and 0.09 and 0.25 nM for (-)N-propylnorapomorphine. After correcting for the fraction of drug bound to plasma proteins, the known clinical concentrations in plasma or plasma water of these drugs, including pramipexole and +PHNO, are sufficient to occupy and activate the high-affinity state of D2, D2(High), in treating Parkinson's disease. The D3(High) receptors are less selectively occupied by +PHNO, bromocriptine, apomorphine, and -NPA.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16088951</PMID><DateCreated><Year>2005</Year><Month>08</Month><Day>15</Day></DateCreated><DateCompleted><Year>2006</Year><Month>03</Month><Day>06</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0887-4476</ISSN><JournalIssue CitedMedium="Print"><Volume>58</Volume><Issue>2</Issue><PubDate><Year>2005</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Synapse (New York, N.Y.)</Title><ISOAbbreviation>Synapse</ISOAbbreviation></Journal><ArticleTitle>Antiparkinson concentrations of pramipexole and PHNO occupy dopamine D2(high) and D3(high) receptors.</ArticleTitle><Pagination><MedlinePgn>122-8</MedlinePgn></Pagination><Abstract><AbstractText>Because the high-affinity state of dopamine D2 receptors, D2(High), is the functional state of D2, and because the proportion of D2 receptors in the high-affinity state correlates with dopamine behavioral supersensitivity, the present study was designed to determine the affinities of antiparkinson dopamine agonists at the D2(High) site by means of competition with [3H]domperidone. In contrast to [125I]iodosulpride or [3H]spiperone, which are not sensitive to low concentrations of dopamine agonists, [3H]domperidone readily reveals dissociation constants (K(i)) for antiparkinson agonists at D2(High) and D3(High) receptors. The K(i) values for the human cloned D2(High) and D3(High) receptors, respectively, were 19 and 9 nM for pramipexole, 0.24 and 0.6 nM for +PHNO, 0.7 and 1.3 nM for bromocriptine, 0.5 and 2.6 nM for apomorphine, and 0.09 and 0.25 nM for (-)N-propylnorapomorphine. After correcting for the fraction of drug bound to plasma proteins, the known clinical concentrations in plasma or plasma water of these drugs, including pramipexole and +PHNO, are sufficient to occupy and activate the high-affinity state of D2, D2(High), in treating Parkinson's disease. 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