Neuroleptic drug interactions with norepinephrine alpha receptor binding sites in rat brain

S. J. Peroutka, D. C. U'Prichard, D. A. Greenberg, S. H. Snyder

Research output: Contribution to journalArticlepeer-review

Abstract

Alpha adrenergic receptor sites in mammalian brain tissue can be labeled by the binding of [3H]WB-4101 (2-([2′,6′-dimethoxy] phenoxyethylamino) methyl benzodioxan), a potent α-adrenergic antagonist. Numerous neuroleptic drugs of phenothiazine, butyrophenone and thioxanthene classes are potent in competing for [3H]WB-4101 binding, with affinities resembling those of classic α-antagonists such as phentolamine and phenoxybenzamine. The potencies of neuroleptics in competing for WB-4101 binding sites correlate closely with their potencies in antagonizing norepinephrine and epinephrine induced lethality in rats, confirming that affinity for WB-4101 binding sites predicts α-receptor antagonism in vivo. The relative affinities of neuroleptics for WB-4101 binding sites and for dopamine receptors as labeled by [3H]haloperidol provides an index of the relative propensities of these drugs for eliciting autonomic side effects such as orthostatic hypotension and sedation.

Original languageEnglish (US)
Pages (from-to)549-556
Number of pages8
JournalNeuropharmacology
Volume16
Issue number9
DOIs
StatePublished - Sep 1977

Keywords

  • Alpha receptor
  • binding
  • hypotension
  • neuroleptics
  • sedation

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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