Pharmacological characterisation of the agonist radioligand binding site of 5-HT2A, 5-HT2B and 5-HT2C receptors

  title={Pharmacological characterisation of the agonist radioligand binding site of 5-HT2A, 5-HT2B and 5-HT2C receptors},
  author={Antony R. Knight and Anil Misra and Kathleen Quirk and Karen R Benwell and Dean F. Revell and Guy A. Kennett and Michael J. Bickerdike},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
In the present study we compared the affinity of various drugs for the high affinity “agonist-preferring” binding site of human recombinant 5-HT2A, 5-HT2B and 5-HT2C receptors stably expressed in monoclonal mammalian cell lines. To ensure that the “agonist-preferring” conformation of the receptor was preferentially labelled in competition binding experiments, saturation analysis was conducted using antagonist and agonist radiolabels at each receptor. Antagonist radiolabels ([3H]-ketanserin for… 

Multiple conformations of 5-HT2A and 5-HT2C receptors in rat brain: an autoradiographic study with [125I](±)DOI

These results conform with the extended ternary complex model of receptor action: receptor exists as an equilibrium of multiple conformations, i.e. ground (R), partly activated (R*) and activated G-protein-coupled (R*G) conformation/s.

Novel Bivalent 5-HT2A Receptor Antagonists Exhibit High Affinity and Potency in Vitro and Efficacy in Vivo.

The 11-atom-linked bivalent 5-HT2AR antagonist (2 mg/kg, intraperitoneally) demonstrated efficacy on par with that of (+)-M100907 in inhibiting cocaine-evoked hyperactivity, and a series of homobivalent ligands connected by ethylene glycol linkers of varying lengths will serve as useful in vitro and in vivo probes of 5- HT2AR structure and function.

Interaction of 5-HT2A and 5-HT2C Receptors in R(−)-2,5-Dimethoxy-4-iodoamphetamine-Elicited Head Twitch Behavior in Mice

Results of these experiments provide strong evidence that DOI-elicited head-twitch behavior is a 5-HT2A agonist-mediated effect, with subsequent inhibition of head- twitch behavior being driven by competing 5- HT2C agonist activity.

The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen

It is concluded that the HTR to DOI in mice is strongly modulated by 5-HT2C receptor activity, a novel finding that invites reassessment of hallucinogenic mechanisms involving 5- HT2 receptors.

5-Hydroxytryptamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Unique amongst the GPCRs, RNA editing produces 5-HT2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to Gq/11 and also pharmacology [40, 482].

The role of 5-HT2A, 5-HT2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice

The 5-HT2AR likely plays a major role in mediating the effects of two tryptamine hallucinogenic drugs and likely modulate the discriminative stimulus effects of both compounds.



[3H]Rauwolscine: an antagonist radioligand for the cloned human 5-hydroxytryptamine2B (5-HT2B) receptor

The usefulness of [3H]rauwolscine as an antagonist radioligand for the cloned human 5-HT2B receptor is displayed and should provide a good tool for the study of both the agonist high- and low-affinity states of the human cloned 5- HT2B receptors.

Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens

Results indicate that an important component of the mechanism of action of LSD and the phenylisopropylamine hallucinogens is through stimulation of brain 5-HT2 receptors, and supports previous suggestions to this effect.

Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, 5-HT2B and 5-HT2C receptors

The present study examined and compared the binding of 17 phenylisopropylamines at human 5- HT2A, 5-HT2B, and 5-Hat2C receptors and found a significant correlation between 5-ht2B receptor affinity and human hallucinogenic potency.

SB 242084, a Selective and Brain Penetrant 5-HT2C Receptor Antagonist

Multiple conformations of native and recombinant human 5-hydroxytryptamine(2a) receptors are labeled by agonists and discriminated by antagonists.

These results conform with the extended ternary complex model of receptor action that postulates the existence of partly activated receptor conformation(s) (R*) in equilibrium with the ground (R) and the activated G protein-coupled (R*G) conformations.

Characterisation of agonist binding on human 5-HT2C receptor isoforms.

Molecular pharmacological differences in the interaction of serotonin with 5-hydroxytryptamine1C and 5-hydroxytryptamine2 receptors.

Observations indicate that guanine nucleotide-binding protein (G protein)-coupled receptors can exhibit high affinity for neurotransmitters in both the free receptor and the G protein- coupled states and that receptors exhibiting this property may represent a novel subfamily of G protein.

Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences.

The cloned human 5-HT2B receptor has high affinity for [3H]5-HT (Kd = 10.6 +/- 1.5 nM), and the pharmacological findings reinforce the desirability of having the human forms of receptors when considering drug actions.

Pharmacological characterisation of human 5-HT2 receptor subtypes.