S(-)DP-5,6-ADTN as an in vivo dopamine receptor ligand

Relation between displacement by dopamine agonists and their pharmacological effects

Hans Rollema, Matthijs G P Feenstra, Cor J. Grol, Mark H. Lewis, Laura Staples, Richard Mailman

Research output: Contribution to journalArticle

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Abstract

The use of (-)DP-5,6-ADTN as a non-radio-actively labeled ligand for an in vivo DA receptor assay is described and compared with racemic DP-5,6-ADTN, previously used for that purpose. The effects of four DA agonists (NPA, bromocriptine, DP-7-OH-ATN and 3-PPP) on the specific (-)DP-5,6-ADTN binding are related to their potencies to decrease striatal HVA concentrations and to induce stereotypy in rats. NPA and DP-7-OH-ATN caused a maximal decrease in HVA levels, when only a fraction of the receptors were occupied, while the occurrence of stereotypy was associated with a high receptor occupation, reflecting the higher affinity of these agonists for presynaptic than for postsynaptic receptors. Bromocriptine did not show this effect, as the dose-response relationships for HVA decrease, for induction of stereotypy and for the decrease in specific (-)DP-5,6-ADTN binding were all virtually equal to each other. While NPA and bromocriptine behaved as full postsynaptic agonists, in that maximal stereotyped behavior was observed after high doses, DP-7-OH-ATN was found to be a partial postsynaptic agonist, as it did not induce maximal stereotypy at a maximal receptor occupation. Racemic 3-PPP only caused a state of hypoactivity, but did neither affect specific (-)DP-5,6-ADTN binding nor striatal HVA levels. Our results are discussed in view of theories on the relation between receptor occupation and pharmacological effects and it is concluded that the in vivo receptor binding method using (-)DP-5,6-ADTN is a very useful tool for such investigations.

Original languageEnglish (US)
Pages (from-to)338-345
Number of pages8
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume332
Issue number4
DOIs
StatePublished - Apr 1 1986

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Dopamine Agonists
Dopamine Receptors
Pharmacology
Ligands
Bromocriptine
Corpus Striatum
Stereotyped Behavior
Presynaptic Receptors
2-amino-5,6-dihydroxytetralin
hydroxide ion

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "S(-)DP-5,6-ADTN as an in vivo dopamine receptor ligand: Relation between displacement by dopamine agonists and their pharmacological effects",
abstract = "The use of (-)DP-5,6-ADTN as a non-radio-actively labeled ligand for an in vivo DA receptor assay is described and compared with racemic DP-5,6-ADTN, previously used for that purpose. The effects of four DA agonists (NPA, bromocriptine, DP-7-OH-ATN and 3-PPP) on the specific (-)DP-5,6-ADTN binding are related to their potencies to decrease striatal HVA concentrations and to induce stereotypy in rats. NPA and DP-7-OH-ATN caused a maximal decrease in HVA levels, when only a fraction of the receptors were occupied, while the occurrence of stereotypy was associated with a high receptor occupation, reflecting the higher affinity of these agonists for presynaptic than for postsynaptic receptors. Bromocriptine did not show this effect, as the dose-response relationships for HVA decrease, for induction of stereotypy and for the decrease in specific (-)DP-5,6-ADTN binding were all virtually equal to each other. While NPA and bromocriptine behaved as full postsynaptic agonists, in that maximal stereotyped behavior was observed after high doses, DP-7-OH-ATN was found to be a partial postsynaptic agonist, as it did not induce maximal stereotypy at a maximal receptor occupation. Racemic 3-PPP only caused a state of hypoactivity, but did neither affect specific (-)DP-5,6-ADTN binding nor striatal HVA levels. Our results are discussed in view of theories on the relation between receptor occupation and pharmacological effects and it is concluded that the in vivo receptor binding method using (-)DP-5,6-ADTN is a very useful tool for such investigations.",
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S(-)DP-5,6-ADTN as an in vivo dopamine receptor ligand : Relation between displacement by dopamine agonists and their pharmacological effects. / Rollema, Hans; Feenstra, Matthijs G P; Grol, Cor J.; Lewis, Mark H.; Staples, Laura; Mailman, Richard.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 332, No. 4, 01.04.1986, p. 338-345.

Research output: Contribution to journalArticle

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AU - Feenstra, Matthijs G P

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AU - Lewis, Mark H.

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AU - Mailman, Richard

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