Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis.
Elaine Sanders‐bush, Kevin D. Burris, Karen M. Knoth
Journal of Pharmacology and Experimental Therapeutics September 1, 1988 DOI: 10.1016/s0022-3565(25)22189-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Population | Rat cerebral cortex and rat choroid plexus |
| Interventions | DOM LSD |
| Topics | LSD Serotonin |
| Keywords | Spiperone Pharmacology Partial agonist Ketanserin Psychotomimetic Phenethylamine 5-HT Receptor 5-ht2 receptor Endocrinology |
| Citations | 155 |
| Key points | DOM and LSD act as partial agonists at 5-HT-2 and 5-HT-1c receptors, with LSD more potent but less efficacious than DOM. |
Abstract
Based on electrophysiological, radioligand binding, and behavioral studies in laboratory animals, it is generally believed that the psychotomimetic effects of the phenethylamine and indolealkylamine hallucinogens are mediated by central serotonin (5-HT) receptors, in particular the 5-HT-2 subtype. Agonist-stimulated phosphoinositide hydrolysis was utilized to determine the potency and efficacy of racemic 1-(2,5)-dimethoxy-4-methyl-phenyl)-2-aminopropane (DOM), and d-lysergic acid diethylamide (LSD) at the 5-HT-2 receptor in rat cerebral cortex and the 5-HT-1c receptor in rat choroid plexus. Both DOM and LSD stimulated phosphoinositide hydrolysis in cerebral cortex. These effects were blocked by the 5-HT-2 antagonists, ketanserin and spiperone, but not by antagonists of muscarinic, alpha-1 adrenergic or histaminergic receptors. The maximum responses of DOM and LSD, respectively, were 76% and 25% of the maximum response to 5-HT. However, LSD was 500 times more potent than was racemic DOM. Consistent with a partial agonist effect, LSD partially blocked the effect of 5-HT, with a maximal inhibition equivalent to the intrinsic activity of LSD alone. In choroid plexus, DOM and LSD stimulated phosphoinositide hydrolysis and both responses were blocked by mianserin and less effectively by spiperone. The maximum effect of DOM was 67% of that of 5-HT, whereas the maximum effect of LSD was only 34% of the maximum response of 5-HT. LSD was 50 times more potent than was racemic DOM. 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparable studies
Other experimental studies on LSD, most cited first.
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|---|---|---|---|
| Neural correlates of the LSD experience revealed by multimodal neuroimaging. Human participants | 2016 | Experimental study | |
| Crystal structure of an LSD-bound human serotonin receptor | 2017 | Experimental study with structural biology and molecular dynamics simulations | |
| Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Midbrain neurons containing serotonin | 1968 | Experimental study | |
| Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Human brain | 2017 | Experimental study | |
| LSD-Assisted Psychotherapy in Patients with Terminal Cancer Cancer patients | 1973 | Experimental study | n = 60 |
Citations in the library
Cited by 75
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- The Pharmacology of Lysergic Acid Diethylamide: A Review CNS Neuroscience & Therapeutics November 11, 2008
- Gender differences in the subjective effects of MDMA Psychopharmacology March 5, 2001
- The promises and perils of psychedelic pharmacology for psychiatry. Nature Reviews Drug Discovery June 1, 2022
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