The action of neuroleptic drugs on dopamine stimulated adenosine cyclic 3',5' monophosphate production in rat neostriatum and limbic forebrain

R. J. Miller, A. S. Horn, L. L. Iversen

Research output: Contribution to journalArticle

237 Scopus citations

Abstract

Neuroleptic drugs of various types were more potent inhibitors of dopamine sensitive production of adenosine 3',5' phosphate (cAMP) in homogenates of rat brain striatum than nonneuroleptic drugs of similar structures. The most potent drugs were phenothiazine and thioxanthene derivatives with a -CF3 group at position 2 of the tricyclic system and a piperazino side chain. There were also large differences in the effects of cis and trans isomers of thioxanthene derivatives, in which the 2 substituent and the side chain are on the same or opposite side of the double bond connecting the side chain to the ring system. Thus α flupentixol, α clopenthixol, and α chlorprothixene, which are the cis isomers, were considerably more potent than the corresponding β isomers of the same drugs. α Flupentixol was also considerably more potent than the β isomer in antagonizing the effect of dopamine on cyclic AMP production in the olfactory tubercle and nucleus accumbens, and in antagonizing the potent dopamine agonist 2 amino 1,2,3,4 tetrahydro 6,7 dihydroxynaphthalene in in the striatum. These results are discussed in relation to the hypothesis that neuroleptic activity may be related to blockade of dopamine receptors in the central nervous system.

Original languageEnglish (US)
Pages (from-to)759-760
Number of pages2
JournalMolecular Pharmacology
Volume10
Issue number5
StatePublished - Jan 1 1974

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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