Differential Binding of Ergot Compounds to Human versus Rat 5-HT₂ Cortical Receptors

Abstract

Eleven ergot compounds were competed against [³H]-ketanserin-labelled 5-HT₂ receptors in rat and human cortex. Four of the ergots are selective for rat 5-HT₂ receptors – mesulergine, methysergide, nicergoline and metergoline, whereas pergolide, d-lysergic acid, ergonovine, ergotamine, d-lysergic acid diethylamide, lisuride and dihydroergotamine display selectivity for human 5-HT₂ receptors. Rat-selective compounds contain a methyl substitution on the indole nitrogen, whereas human-selective compounds contain a hydrogen. This structural feature may allow the two groups of ergots to differentiate between the two species of receptors.

Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. III. Agonist and Antagonist Properties at Serotonin, 5-HT1 and 5-HT2, Receptor Subtypes

“…Using the complementary approach of depletion of membrane-bound [ 3 H]PI (Cussac et al, 2002b), bromocriptine similarly activated phospholipase C at h5-HT 2A receptors, consistent with its high affinity for h5-HT 2A (Porter et al, 1999;Egan et al, 2000;Jerman et al, 2001). Like lisuride, a further ergot possessing high affinity for 5-HT 2A sites, pergolide (Hagen et al, 1994;Millan et al, 2002), was an efficacious agonist at h5-HT 2A receptors, actions mimicked by terguride and cabergoline. In contrast, the structurally distinct roxindole, a potent ligand of h5-HT 2A sites , and apomorphine behaved as antagonists at h5-HT 2A receptors, whereas piribedil was inactive.…”

Pharmacological and behavioral characterization of the 5-HT2A receptor in C57BL/6N mice

“…Additionally, the relationship between 5-HT 2A and the closely related 5-HT 2C receptor densities in cortex and frontal cortex was examined. Whole Fone et al 1998;Hoyer et al 1985Hoyer et al , 1986Hulihan-Giblin et al 1994;Leonhardt et al 1992;Pranzatelli andBalletti 1992 b Schindler et al, unpublished c Hoyer et al 1985;Leonhardt et al 1992;Pazos et al 1985;Pranzatelli and Balletti 1992 d Battaglia et al 1983Battaglia et al , 1984Bonhaus et al 1995;Hagen et al 1994;Johnson et al 1996;Leonhardt et al 1992;Leysen et al 1982Leysen et al , 1988Lyon et al 1987;Meltzer et al 1989;Neale et al 1987;Nelson et al 1993;Pazos et al 1984;Rinaldi-Carmona et al 1992;Roth et al 1992;Sadzot et al 1989;Schotte et al 1983;Schreiber et al 1995;Wainscott et al 1996 c Aloyo andHarvey 2000, Schindler et al, unpublished;Weber et al 1997 d Bonhaus et al 1995;Hagen et al 1994;López-Giménez et al 1998;Nelson et al 1993;Pazos et al 1984;Sadzot et al 1989;Schotte et al 1983 -Giménez et al 2002), respectively. In addition to similarities to autoradiography results, the number of DOI-elicited HTRs in C57BL/6N mice in t...…”

Blockade of serotonin 5-HT 1B and 5-HT 2A receptors suppresses the induction of locomotor activity by 5-HT reuptake inhibitors, citalopram and fluvoxamine, in NMRI mice exposed to a novel environment: a comparison to other 5-HT receptor subtypes

“…Third, MDL100,907 and ketanserin attenuated the locomotor actions of cocaine in rats though data are conflicting as concerns their interference with stimulation of LA by a further psychostimulant, amphetamine (Millan et al 1999a;McMahon and Cunningham 2001a;Munzar et al 2002). Fourth, 5-HT 2A receptors are involved in the induction of LA by the "dopaminergic" agonist, pergolide, which displays agonist properties at 5-HT 2A receptors (Hagen et al 1994;Moore et al 1999). Finally, MDL100,907 attenuated the LA elicited in rats by the open channel blocker at NMDA receptors, PCP (Millan et al 1999a), without modifying its influence on extracellular 5-HT: comparable observations were made here with citalopram.…”