Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens.
M Titeler, R A Lyon, Richard A Glennon
Psychopharmacology 1988 DOI: 10.1007/bf00176847 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro radioligand binding study Peer reviewed |
|---|---|
| Population | Radiolabelled serotonin receptor subtypes (5-HT2, 5-HT1A, 5-HT1B, 5-HT1C) in in vitro preparations |
| Topics | LSD Serotonin |
| Key points | Phenylisopropylamine hallucinogens bound with 10-100 fold higher affinity to 5-HT2 than 5-HT1C receptors and 100-1000 fold higher affinity than to 5-HT1A or 5-HT1B receptors. Hallucinogenic potency correlated strongly with 5-HT2 affinity (r = 0.90). The authors argue this implicates 5-HT2 receptor interaction in hallucinogen action, while not discounting a secondary role for 5-HT1C receptors. |
Abstract
Alterations in brain serotonergic function have been implicated in the mechanism of action of LSD, mescaline, and other similarly acting hallucinogenic drugs of abuse such as STP (2,5-dimethoxyphenylisopropylamine; DOM). In order to test the hypothesis that the mechanism of action of LSD and phenylisopropylamine hallucinogens is through stimulation of a specific brain serotonin receptor sub-type, the affinities of these compounds for radiolabelled 5-HT2, 5-HT1A, 5-HT1B, and 5-HT1C receptors have been determined using recently developed in vitro radioligand binding methodologies. The 5-HT2 receptor was labelled with the agonist/hallucinogen radioligand 3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine). The 5-HT1A, 5-HT1B, and 5-HT1C receptors were labelled with 3H-OH-DPAT, 3H-5-HT, and 3H-mesulergine, respectively. In general, the phenylisopropylamines displayed 10-100 fold higher affinities for the 5-HT2 receptor than for the 5-HT1C receptor and 100-1000 fold higher affinities for the 5-HT2 receptor than for the 5-HT1A or 5-HT1B receptor. There was a strong correlation between hallucinogenic potencies and 5-HT2 receptor affinities of the phenylisopropylamines (r = 0.90); the correlation coefficients for the 5-HT1A, 5-HT1B, and 5-HT1C were 0.73, 0.85, and 0.78, respectively. Because there is no evidence that 5-HT1A-selective or 5-HT1B-selective agonists are hallucinogenic and because the phenylisopropylamines are potent hallucinogens, a 5-HT2 receptor interaction is implicated and supports our previous suggestions to this effect. A secondary role for 5-HT1C receptors cannot be discounted at this time.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
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- 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Journal of Neuroscience April 15, 1997
- Crystal structure of an LSD-bound human serotonin receptor Cell January 26, 2017
- The Pharmacology of Lysergic Acid Diethylamide: A Review CNS Neuroscience & Therapeutics November 11, 2008
- Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Biological Psychiatry November 29, 2014
and 139 more in the library
Cites 5
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Science August 16, 1968
- 3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) labels a guanyl nucleotide-sensitive state of cortical 5-HT2 receptors. Molecular Pharmacology February 1, 1987
- Lysergic Acid Diethylamide New England Journal of Medicine February 22, 1968
- Site-selective serotonin agonists as discriminative stimuli. Psychopharmacology series 1988