Theoretical studies on the interaction of partial agonists with the 5-HT2A receptor

  title={Theoretical studies on the interaction of partial agonists with the 5-HT2A receptor},
  author={Maria Elena Silva and Ralf Heim and Andrea Strasser and Sigurd Elz and Stefan Dove},
  journal={Journal of Computer-Aided Molecular Design},
A series of 51 5-HT2A partial agonistic arylethylamines (primary or benzylamines) from different structural classes (indoles, methoxybenzenes, quinazolinediones) was investigated by fragment regression analysis (FRA), docking and 3D-QSAR approaches. The data, pEC50 values and intrinsic activities (Emax) on rat arteries, show high variability of pEC50 from 4 to 10 and of Emax from 15 to 70%. FRA indicates which substructures affect potency or intrinsic activity. The high contribution of halogens… 

5-HT2 receptor binding, functional activity and selectivity in N-benzyltryptamines

Although some N-benzyltryptamines might be abuse-liable, others might represent new leads for the development of therapeutics for weight loss, erectile dysfunction, drug abuse, or schizophrenia.

Dibenzofuranylethylamines as 5-HT2A/2C Receptor Agonists

Five phenethylamine analogs in which the benzene ring is replaced by a bulky dibenzo[b,d]furan moiety are synthesized and found a couple with >70-fold 5-HT2C selectivity.

N-Benzyl-5-methoxytryptamines as Potent Serotonin 5-HT2 Receptor Family Agonists and Comparison with a Series of Phenethylamine Analogues

A series of N-benzylated-5-methoxytryptamine analogues was prepared and investigated, with special emphasis on substituents in the meta position of the benzyl group, revealing a significant correlation between this behavior and functional potency at the rat 5-HT2A receptor.

NBOMes–Highly Potent and Toxic Alternatives of LSD

An updated overview of the pharmacological properties, pattern of use, metabolism, and desired effects associated with NBOMe use is provided and the analytical methods most commonly used for detection and identification of NBOMes and their metabolites are presented.

Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens.

  • A. Halberstadt
  • Chemistry, Biology
    Current topics in behavioral neurosciences
  • 2017
Based on a review of 51 cases of NBOMe toxicity reported in the literature, it appears that rhabdomyolysis is a relatively common complication of severe NBOME toxicity, an effect that may be linked toNBOMe-induced seizures, hyperthermia, and vasoconstriction.

25B-NBOMe and its precursor 2C-B: modern trends and hidden dangers

Substituted phenethylamines are a class of designer drugs that hold a significant position in the drug abuse market. The most important substances within this class appear to be

Analytical characterization of four new ortho-methoxybenzylated amphetamine-type designer drugs.

Four N-(ortho-methoxybenzyl)amines with amphetamine partial structure were obtained as pure compounds and have been detected in Germany for the first time and no analytical data had been previously published.

Analytical characterization of three hallucinogenic N-(2-methoxy)benzyl derivatives of the 2C-series of phenethylamine drugs.

Analytical properties of three new hallucinogenic substances identified in blotter papers seized from the drug market are reported, which are N-(2-methoxy)benzyl derivatives of the 2C-series of phenethylamine drugs.



Molecular Interaction of Serotonin 5-HT2A Receptor Residues Phe339(6.51) and Phe340(6.52) with Superpotent N-Benzyl Phenethylamine Agonists

This study is the first to identify a hitherto unrecognized role for residue 6.51 in agonist activation of a serotonin G protein-coupled receptor (GPCR), whereas most previous reports have suggested a varied and sometimes contradictory role in homologous GPCRs.

Mapping the Binding Site Pocket of the Serotonin 5-Hydroxytryptamine2A Receptor

Findings identify a mode of ligand-receptor complexation that involves two receptor side chains interacting with the same functional group of specific serotonergic ligands that serves to orient the ligands in the binding pocket and may influence the degree of receptor activation.

Differential modes of agonist binding to 5-hydroxytryptamine(2A) serotonin receptors revealed by mutation and molecular modeling of conserved residues in transmembrane region 5.

The results suggest that relatively minor changes in either receptor or ligand structure can produce drastic and unpredictable changes in both binding interactions and 5-HT(2A) receptor activation.

Species variations in transmembrane region V of the 5-hydroxytryptamine type 2A receptor alter the structure-activity relationship of certain ergolines and tryptamines.

Arguments are presented that suggest that a hydrogen-bonding interaction occurs between the human 5-HT2A receptor at Ser242 and the N1-hydrogen of N 1-unsubstituted ergolines and tryptamines and may serve as an important contact point in the receptor.

Site-directed mutagenesis of the serotonin 5-hydroxytrypamine2 receptor: identification of amino acids necessary for ligand binding and receptor activation.

Results indicate that Asp-120 is necessary for allosteric activation of the guanine nucleotide-binding protein in the 5-HT2 receptor, probably by acting as a counterion for the amine group of the ligand.

5-Hydroxytryptamine receptor subtypes.

  • S. Peroutka
  • Biology, Chemistry
    Pharmacology & toxicology
  • 1990
In order to provide a comparative pharmacological analysis of the 7 most extensively characterized 5-HT receptor subtypes, potency information is presented on the 30 pharmacological agents that have been, to date, studied most extensively in the published literature.

Related Contribution of Specific Helix 2 and 7 Residues to Conformational Activation of the Serotonin 5-HT2A Receptor (*)

The additive effects of mutations at this locus and at a conserved helix 7 locus investigated in the 5-HT2A receptor suggest that these residues are adjacent in space and interact and implicate both loci in a common hydrogen-bonding network underlying receptor activation by agonist.

High-affinity agonist binding is not sufficient for agonist efficacy at 5-hydroxytryptamine2A receptors: evidence in favor of a modified ternary complex model.

The ability of an agonist to promote the high-affinity state of the 5-hydroxytryptamine2A receptor is not correlated with its ability to augment second messenger production, consistent with recent models of G protein-receptor functioning.

Pharmacological Profile of Histaprodifens at Four Recombinant Histamine H1 Receptor Species Isoforms

The aim of this study was to analyze species differences in more detail, focusing on histaprodifen derivatives and including the bovine histamines H1 receptor (bH1R) and rat histamine H1 receptors (rH1S) and to conclude that chiral histap Rodifens interact differentially with H1R species isoforms.