Dopamine receptor stimulating effects of chanoclavine analogues, tricyclic ergot alkaloids, in the brain

Jpn J Pharmacol. 1987 Dec;45(4):501-6. doi: 10.1254/jjp.45.501.

Abstract

The abilities of tricyclic ergot alkaloids, chanoclavine-I and its analogues, and bromocriptine to stimulate dopamine receptors in the brain were investigated. Receptor binding of 3H-spiperone has shown that bromocriptine exhibits clear affinity for this compound. The order of displacement potencies was bromocriptine much greater than ergometrine, KSU-1415 greater than chanoclavine-I, KSU-1118, KSU-1791. In the striatum of mice treated with an amino acid decarboxylase inhibitor, gamma-butyrolactone-induced DOPA accumulation was markedly inhibited by bromocriptine and KSU-1415, but not inhibited by chanoclavine-I. In mice with unilateral striatal 6-hydroxydopamine lesions, bromocriptine and KSU-1415 produced a long-lasting contralateral rotation that was suppressed by prior treatment with (+/-)-sulpiride. These results suggest that a tricyclic ergot alkaloid of the chanoclavine type stimulates D-2 receptors in the brain.

MeSH terms

  • 4-Butyrolactone / metabolism
  • Animals
  • Binding, Competitive / drug effects
  • Brain / drug effects
  • Brain / metabolism*
  • Catechols / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dihydroxyphenylalanine / metabolism
  • Ergolines / pharmacokinetics
  • Ergolines / pharmacology*
  • Ergot Alkaloids / pharmacology
  • In Vitro Techniques
  • Male
  • Mice
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Rotation
  • Spiperone / metabolism
  • Stereotyped Behavior / drug effects
  • Time Factors

Substances

  • Catechols
  • Ergolines
  • Ergot Alkaloids
  • Receptors, Dopamine
  • chanoclavine
  • Spiperone
  • Dihydroxyphenylalanine
  • 4-Butyrolactone