A pharmacological analysis of the effects of (+)-AJ 76 and (+)-UH 232 at release regulating pre- and postsynaptic receptors

Andrew N. Gifford, Kenneth M. Johnson

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

To examine the proposal that (+)-AJ 76 and (+)-UH 232 are dopamine receptor antagonists showing preference for the dopamine autoreceptors over postsynaptic dopamine receptors, the potencies of these two compounds, as well as several typical and atypical antipsychotic drugs, were compared in a model for presynaptic dopamine autoreceptors: reversal of the quinpiroleinduced inhibition of [3H]dopamine release from striatal slices, and in two models for postsynaptic dopamine receptors: reversal of the quinpirole-induced inhibition of [14C]acetylcholine release from striatal slices and competition for [3H]spiperone binding in striatal homogenates. The IC50 values of the antipsychotic drugs, as well as (+)-AJ 76 and (+)-UH 232, againts [2H]dopamine release correlated closely with their IC50 values against [14C]acetylcholine release and Ki values againts [3H]spiperone binding, thus suggesting a close pharmacological similarity between these three populations of dopamine receptors. This implies that previous biochemical and behavioral findings obtained with (+)-AJ 76 and (+)-UH 232 cannot be explained by a selective action of these compounds on terminal dopamine autoreceptors regulating dopamine release, at least relative to the postsynaptic dopamine receptors on cholinergic neurons. Furthermore, comparison of the IC50 values for teh drugs tested in our transmitter release assays with previously published values of their affinity for cloned dopamine D2, D3 and D4 receptors suggested that the dopamine receptors controlling both dopamine and acetylcholine release were by far most similar to dopamine D2 receptors.

Original languageEnglish (US)
Pages (from-to)169-175
Number of pages7
JournalEuropean Journal of Pharmacology
Volume237
Issue number2-3
DOIs
StatePublished - Jun 24 1993

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Presynaptic Receptors
Dopamine
Dopamine Receptors
Pharmacology
Corpus Striatum
Autoreceptors
Inhibitory Concentration 50
Acetylcholine
Spiperone
Dopamine D2 Receptors
Antipsychotic Agents
Dopamine D4 Receptors
Dopamine D3 Receptors
Quinpirole
Cholinergic Neurons
Dopamine Antagonists
5-methoxy-1-methyl-2-(n-propylamino)tetralin
UH 232
Pharmaceutical Preparations

Keywords

  • Acetylcholine release
  • AJ 76
  • Antipsychotics
  • Dopamine receptors
  • Striatum
  • UH 232

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

A pharmacological analysis of the effects of (+)-AJ 76 and (+)-UH 232 at release regulating pre- and postsynaptic receptors. / Gifford, Andrew N.; Johnson, Kenneth M.

In: European Journal of Pharmacology, Vol. 237, No. 2-3, 24.06.1993, p. 169-175.

Research output: Contribution to journalArticle

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