(+)-AJ 76 and (+)-UH 232: central stimulants acting as preferential dopamine autoreceptor antagonists

Naunyn Schmiedebergs Arch Pharmacol. 1986 Nov;334(3):234-45. doi: 10.1007/BF00508777.


The biochemical and behavioral effects of the putative dopamine autoreceptor antagonists cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76 and cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, were evaluated in various in vivo models in rats. Both compounds produced a marked elevation in brain dopamine synthesis and turnover with only slight effects on the synthesis and turnover of serotonin (5-HT) and noradrenaline being noted. (+)-AJ 76 and (+)-UH 232 also failed to antagonize the decrease in cortical noradrenaline synthesis rate caused by the alpha 2 agonist clonidine. The apomorphine-induced decrease in dopamine synthesis rate in gamma-butyrolactone (GBL) treated animals was completely blocked by (+)-AJ 76 and (+)-UH 232 but not by d-amphetamine or methylphenidate. In activity experiments using habituated animals, (+)-AJ 76 and (+)-UH 232 produced locomotor stimulation and weak stereotypies and antagonized the sedative effects of low doses of apomorphine. Locomotor hyperactivity induced by apomorphine or the dopamine agonist DiPr-5,6-ADTN was antagonized by (+)-UH 232 and to a lesser degree by (+)-AJ 76. The locomotor hyperactivity produced by (+)-AJ 76, (+)-UH 232 and methylphenidate was completely prevented by reserpine pretreatment and partially blocked by the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (alpha-MT), whereas d-amphetamine-induced hyperactivity was only antagonized by alpha-MT pretreatment. It is concluded that (+)-AJ 76 and (+)-UH 232 produce behavioral stimulation via a preferential antagonism on central dopamine autoreceptors, an action different from that of all known stimulants including apomorphine, d-amphetamine and methylphenidate. (+)-AJ 76 and (+)-UH 232 possess but weak antagonistic effects on postsynaptic dopamine receptors and only the latter compound is able to induce sedation in rats.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / pharmacology
  • 8-Hydroxy-2-(di-n-propylamino)tetralin* / analogs & derivatives*
  • Animals
  • Apomorphine / antagonists & inhibitors
  • Brain / drug effects*
  • Brain / metabolism
  • Male
  • Methyltyrosines / pharmacology
  • Motor Activity / drug effects
  • Naphthalenes / pharmacology*
  • Neurotransmitter Agents / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / metabolism
  • Reserpine / pharmacology
  • Tetrahydronaphthalenes / antagonists & inhibitors
  • Tetrahydronaphthalenes / pharmacology*


  • Methyltyrosines
  • Naphthalenes
  • Neurotransmitter Agents
  • Receptors, Dopamine
  • Tetrahydronaphthalenes
  • alpha-methyltyrosine methyl ester
  • 2-(N,N-dipropyl)amino-5,6-dihydroxytetralin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • 5-methoxy-1-methyl-2-(n-propylamino)tetralin
  • Reserpine
  • UH 232
  • Apomorphine
  • 4-Butyrolactone