The putatively selective dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 stimulate prolactin release in rats

Eur J Pharmacol. 1986 Nov 4;130(3):237-42. doi: 10.1016/0014-2999(86)90273-6.

Abstract

The 2-aminotetralin derivatives cis-(+)-(1S,2R)-5-methoxyl-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76, and cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, are novel centrally acting stimulants with a putative action as selective dopamine (DA) autoreceptor antagonists. In the present study these compounds were evaluated with respect to their effects on prolactin release in male rats. Both (+)enantiomers caused a pronounced increase in plasma prolactin levels in previously untreated animals. The effects of (+)-AJ 76 and (+)-UH 232 were virtually similar, except for a higher initial increase after the latter compound. In agreement with earlier reports, the reserpine-induced elevation of plasma levels of prolactin was strongly suppressed by the DA autoreceptor agonist B-HT 920. This effect of B-HT 920 was completely blocked by (+)-AJ 76 and by (+)-UH 232, indicating that both (+)enantiomers antagonize lactotroph DA receptors. The present findings support the notion that lactotroph DA receptors resemble DA autoreceptors rather than postsynaptic DA receptors. A possible difference between the auto-/lactotroph vs. postsynaptic DA receptors with respect to both the responsiveness to agonists and to the affinity of pure antagonists is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin* / analogs & derivatives*
  • Animals
  • Azepines / pharmacology
  • Male
  • Naphthalenes / pharmacology*
  • Prolactin / blood
  • Prolactin / metabolism*
  • Radioimmunoassay
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Reserpine / pharmacology
  • Tetrahydronaphthalenes / pharmacology*

Substances

  • Azepines
  • Naphthalenes
  • Receptors, Dopamine
  • Tetrahydronaphthalenes
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • talipexole
  • 5-methoxy-1-methyl-2-(n-propylamino)tetralin
  • Reserpine
  • Prolactin
  • UH 232