LSD and structural analogs: pharmacological evaluation at D1 dopamine receptors.
V J Watts, C P Lawler, D R Fox, K A Neve, D E Nichols, R B Mailman
Psychopharmacology April 1995 DOI: 10.1007/bf02245940 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro receptor binding and functional study Peer reviewed |
|---|---|
| Population | Rat striatal tissue and C-6 glioma cells expressing the rhesus macaque D1A receptor |
| Topics | LSD |
| Key points | LSD and several lysergamide analogs bound both D1-like and D2-like dopamine receptors in rat striatum with agonist-like binding profiles. Their affinity for D2-like receptors was similar to their affinity for serotonin 5HT2 sites, while D1-like affinity was two- to threefold lower; LSD and several analogs bound D1 receptors with affinity similar to the prototypical D1 partial agonist SKF38393 (K0.5 about 25 nM). |
Abstract
The hallucinogenic effects of lysergic acid diethylamide (LSD) have been attributed primarily to actions at serotonin receptors. A number of studies conducted in the 1970s indicated that LSD also has activity at dopamine (DA) receptors. These latter studies are difficult to interpret, however, because they were completed before the recognition of two pharmacologically distinct DA receptor subtypes, D1 and D2. The availability of subtype-selective ligands (e.g., the D1 antagonist SCH23390) and clonal cell lines expressing a homogeneous receptor population now permits an assessment of the contributions of DA receptor subtypes to the DA-mediated effects of LSD. The present study investigated the binding and functional properties of LSD and several lysergamide and analogs at dopamine D1 and D2 receptors. Several of these compounds have been reported previously to bind with high affinity to serotonin 5HT2 (i.e., 3H-ketanserin) sites in the rat frontal cortex (K0.5 5-30 nM). All tested compounds also competed for both D1-like (3H-SCH 23390) and D2-like (3H-spiperone plus unlabeled ketanserin) DA receptors in rat striatum, with profiles indicative of agonists (nH < 1.0). The affinity of LSD and analogs for D2 like receptors was similar to their affinity for 5HT2 sites. The affinity for D1 like receptors was slightly lower (2- to 3-fold), although LSD and several analogs bound to D1 receptors with affinity similar to the prototypical D1 partial agonist SKF38393 (K0.5 ca. 25 nM). A second series of experiments tested the binding and functional properties of LSD and selected analogs in C-6 glioma cells expressing the rhesus macaque D1A receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
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- Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology December 1, 2015
- The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial Psychopharmacology November 26, 2018
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Cites 10
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- Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives Journal of Medicinal Chemistry September 1, 1985
- Serotonin and the Action of LSD in the Brain Psychiatric Annals March 1, 1994
- Stereoselective LSD-like activity in d-lysergic acid amides of R- and S-2-aminobutane Journal of Medicinal Chemistry 1992
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