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

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

Research output: Contribution to journalArticle

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 - 1977

Fingerprint

Drug Interactions
Adrenergic Receptors
Antipsychotic Agents
Binding Sites
Brain
Thioxanthenes
Butyrophenones
Autonomic Agents
Receptors, Adrenergic, alpha
Phenoxybenzamine
Orthostatic Hypotension
Adrenergic Antagonists
Phentolamine
Dopamine Receptors
Haloperidol
Epinephrine
Norepinephrine
(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
Pharmaceutical Preparations

Keywords

  • Alpha receptor
  • binding
  • hypotension
  • neuroleptics
  • sedation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Neuroleptic drug interactions with norepinephrine alpha receptor binding sites in rat brain. / Peroutka, S. J.; U'Prichard, D. C.; Greenberg, D. A.; Snyder, Solomon H.

In: Neuropharmacology, Vol. 16, No. 9, 1977, p. 549-556.

Research output: Contribution to journalArticle

Peroutka, S. J. ; U'Prichard, D. C. ; Greenberg, D. A. ; Snyder, Solomon H. / Neuroleptic drug interactions with norepinephrine alpha receptor binding sites in rat brain. In: Neuropharmacology. 1977 ; Vol. 16, No. 9. pp. 549-556.
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