Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors

  title={Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors},
  author={C T Egan and Katharine Herrick‐Davis and Keith J. Miller and Richard A Glennon and Milt Teitler},
Abstract Evidence from studies with phenylisopropylamine hallucinogens indicates that the 5HT2A receptor is the likely target for the initiation of events leading to hallucinogenic activity associated with LSD and related drugs. Recently, lisuride (a purported non-hallucinogenic congener of LSD) was reported to be a potent antagonist at the 5HT2C receptor and an agonist at the 5HT2A receptor. LSD exhibited agonist activity at both receptors. These data were interpreted as indicating that the… 

LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT2A receptor

It is demonstrated that lisuride and LSD disrupt PPI via distinct receptor mechanisms and provide additional support for the classification of l isuride as a non-hallucinogenic 5-HT2A agonist.

Re-evaluation of lisuride pharmacology: 5-hydroxytryptamine1A receptor-mediated behavioral effects overlap its other properties in rats

It is demonstrated that the behavioral effects of low doses of lisuride are clearly mediated by stimulation of 5-HT1A receptors.

The 5-HT1A receptor and the stimulus effects of LSD in the rat

Data obtained using a drug discrimination model of the hallucinogenic effects of LSD provide support for the hypothesis that the 5-HT1A receptor has a significant modulatory role in the stimulus effects ofLSD.

8R-lisuride is a potent stereospecific histamine H1-receptor partial agonist.

8R-lisuride is the most potent stereospecific partial agonist for the human H1R yet reported, and provides a valuable tool to further characterize this important therapeutic target in vitro.

Functional Selectivity of Hallucinogenic Phenethylamine and Phenylisopropylamine Derivatives at Human 5-Hydroxytryptamine (5-HT)2A and 5-HT2C Receptors

The results support the concept of functional selectivity and indicate that subtle changes in ligand structure can result in significant differences in the cellular signaling profile.

Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

ecent advances in the neuropsychopharmacology of serotonergic allucinogens

The evidence demonstrating the serotonin 5-HT2A receptor is the primary site of hallucinogen action is reviewed, showing it to be responsible for mediating the effects of hallucinationsinogens in human subjects and in animal behavioral paradigms.

Serotonin type 5A receptor antagonists inhibit D-lysergic acid diethylamide discriminatory cue in rats

The present results suggest that antagonists of the 5-HT5A receptor may inhibit subjective effects of LSD in rats.



(+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist.

The present finding that (+)LSD, but not its nonhallucinogenic congeners, is a 5HT1C receptor agonist suggests a possible role for these receptors in mediating the psychoactive effects of LSD.

Pharmacological characteristics of the newly cloned rat 5-hydroxytryptamine2F receptor.

The affinity of a compound for the 5-HT2F receptor at 37 degrees versus 0 degree was shown to be useful for predicting agonist or antagonist activity, and information is provided about some of the structural requirements for the affinity of certain tryptamines at the 4-HT/1C receptor family.

LSD and the phenethylamine hallucinogen DOI are potent partial agonists at 5-HT2A receptors on interneurons in rat piriform cortex.

It is concluded that LSD and DOI, a phenethylamine hallucinogen, act as highly potent partial agonists at cortical 5-HT2A receptors at rat piriform cortical interneurons.

Constitutively active 5-hydroxytryptamine2C receptors reveal novel inverse agonist activity of receptor ligands.

Evidence is provided that constitutively active 5-HT2C receptors are biologically significant and the functionally distinct properties of inverse agonists and neutral antagonists may elucidate the mechanisms controlling basal receptor activity states and lead to novel approaches in the development of therapeutic agents.

Comparative effects of LSD and lisuride: Clues to specific hallucinogenic drug actions

  • F. J. White
  • Biology, Psychology
    Pharmacology Biochemistry and Behavior
  • 1986

Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents.

Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis.

LSD partially antagonized the effect of 5-HT in the choroid plexus, consistent with a partial agonist effect at the 5- HT-1c receptor in this tissue.

Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors.

The authors examined the affinities of 36 typical and atypical antipsychotic agents for the cloned rat 5-hydroxytryptamine-6 and rat5-HT7 receptors in transiently expressed COS-7 cells or stably transfected HEK-293 cells to identify those with high affinity for the newly discovered 5-HT6 receptor.