Physiol. Res. 53: 35-43, 2004

Pergolide, Terguride and N,N'-spacer-linked Oligomers of Both Interact with 5-HT2A Receptors of Rat Tail Artery


Institute of Microbiology, Laboratory of Biotransformation, Academy of Sciences of the Czech Republic, Prague, Czech Republic, 1Institut für Pharmazie, Freie Universität Berlin, Germany

Received November 5, 2002
Accepted February 27, 2003

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.

Key words
Pergolide • Terguride • Oligomers of pergolide and terguride • 5-HT2A receptors • Contraction • Rat tail artery

© 2004 by the Institute of Physiology, Czech Academy of Sciences