Pergolide, terguride and N,N'-spacer-linked oligomers of both interact with 5-HT2A receptors of rat tail artery

Physiol Res. 2004;53(1):35-43.

Abstract

Pergolide, terguride and N,N'-spacer-linked oligomers of both have been tested for their ability to interact with 5 hydroxytryptamine(HT)2A receptors of rat tail artery. Pergolide was a potent partial agonist (pEC50 7.5, Emax 55 %) and antagonized 5-HT-induced contractions (pKp 7.2). Pergolide dimer 3 with a p-xylene spacer between the indole nitrogens (N-1) displayed somewhat lower agonist potency than pergolide (pEC50 7.0, Emax 55 %, pKp 6.6). The contractile responses to pergolide and dimer 3 were antagonized by the 5-HT2A receptor antagonist ketanserin (pA2 9.4, 9.1). In contrast to pergolide dimer 3, pergolide dimers 5 and 9 with an alkyl and an aralkyl spacer between the piperidine nitrogens (N-6) lacked agonism and displayed low affinity at 5-HT2A receptors (pA2 < 5.5). Terguride behaved as an insurmountable antagonist of 5-HT (pA2 8.4). Oligomers of terguride showed 5 to 50-fold lower affinity. It is concluded that pergolide and terguride show a high affinity for 5-HT2A receptors, but dimerization (oligomerization) of both drugs fails to increase affinity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / drug effects*
  • Arteries / metabolism
  • Dimerization
  • Dopamine Agonists / chemistry
  • Dopamine Agonists / metabolism
  • Dopamine Agonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Lisuride / analogs & derivatives*
  • Lisuride / chemistry
  • Lisuride / metabolism
  • Lisuride / pharmacology*
  • Male
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Pergolide / chemistry
  • Pergolide / metabolism
  • Pergolide / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Serotonin / pharmacology
  • Tail / blood supply
  • Vasoconstriction / drug effects

Substances

  • Dopamine Agonists
  • Peptide Fragments
  • Receptor, Serotonin, 5-HT2A
  • dironyl
  • Pergolide
  • Serotonin
  • Lisuride