Binding to the serotonin 5-HT2 receptor by the enantiohers of 125I-DOI

  title={Binding to the serotonin 5-HT2 receptor by the enantiohers of 125I-DOI},
  author={M. P. Johnson and Andrew J. Hoffman and David E. Nichols and Chester A. Mathis},

Structure–Activity Relationships of Phenylalkylamines as Agonist Ligands for 5‐HT2A Receptors

This review summarizes the structure–activity relationships (SAR) of phenylalkylamines as agonist ligands for 5‐HT2A receptors and selectivity is a central theme, as is selectivity for the 5‐ HT2A receptor and for its specific signaling pathways.

A novel (benzodifuranyl)aminoalkane with extremely potent activity at the 5-HT2A receptor.

Rat behavioral data and human receptor binding data showed that 2 is more potent than 1, a finding that was consistent with a binding site model first postulated by Westkaemper and Glennon, in which two hydrogenbond-donor residues in the receptor lie on opposite sides of the molecule and form hydrogen bonds with the ether oxygen lone pairs.

Structure–activity relationships of serotonin 5‐HT2A agonists

Important structural features are identified for agonist activity and some of these agonists have features in common and in addition to effects at the receptor will be the focus, these drugs are also hallucinogenic (psychedelic) agents, and much of the SAR was developed on the basis of effects in humans, before modern pharmacological techniques were available.

Differential phospholipase C activation by phenylalkylamine serotonin 5‐HT2A receptor agonists

The hypothesis that phenylisopropylamines have higher hallucinogenic potency than their phenethylamine analogues primarily because they have higher intrinsic activities at 5‐HT2A receptors is supported.

Stereoselective LSD-like activity in d-lysergic acid amides of (R)- and (S)-2-aminobutane.

It is concluded that the conformation of the amide function may directly affect binding through stereoselective interactions with a hydrophobic region on the receptor, indirectly by inducing conformational changes elsewhere in the molecule, or by a combination of these two mechanisms.

Effect of a chiral 4-alkyl substituent in hallucinogenic amphetamines.

Evaluating changes in behavioral and biochemical pharmacology resulting from introducing chirality into the 4-alkyl group of hallucinogenic amphetamine derivatives found that two diastereoisomeric derivatives containing a 4-(R or S)-2-butyl substituent may differ in their receptor agonist efficacy from more behaviorally active compounds such as 2.



3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) labels a guanyl nucleotide-sensitive state of cortical 5-HT2 receptors.

3H-DOB labels a subset of brain 5-HT2 receptors that has high affinity for agonists as well as antagonists); 3H-ketanserin appears to label both subsets ofbrain 5- HT2 receptors.

Guanyl Nucleotide and Divalent Cation Regulation of Cortical S2 Serotonin Receptors

Computer‐assisted quantitative analysis of radioligand binding to rat cortical S2 serotonin receptors indicates the existence of two affinity states of the same receptor population, the first evidence suggesting involvement of a guanine nucleotide‐binding protein in the mechanism of agonist interaction with the S, serotonin receptor.

Guanine nucleotides modulate cortical S2 serotonin receptors.

The agonists serotonin, 5-methoxytryptamine, bufotenine, and tryptamine display threefold lower affinities for S2 serotonin receptors in the presence of 10(-4)M GTP or Gpp(NH)p than in the absence of the nucleotides.