Stereospecific receptor sites for d-lysergic acid diethylamide in rat brain: effects of neurotransmitters, amine antagonists, and other psychotropic drugs.
Richard A. Lovell, Daniel X. Freedman
Molecular Pharmacology July 1, 1976 DOI: 10.1016/s0026-895x(25)10797-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Rat brain particulates |
| Topics | LSD |
| Citations | 54 |
| Key points | The high-affinity, stereospecific binding site for d-LSD on rat brain membranes may not be identical with a serotonin or dopamine receptor, but LSD can bind to such receptors while also attaching to nearby membrane points. |
Abstract
A method in vitro designed to determine specifically the stereospecificity of tissue receptor sites was used to study the characteristics of d-lysergic acid diethylamide (LSD) binding by rat brain particulates and the effects of selectively chosen drugs. There is a high- and a low-affinity binding, and both are stereospecific. The high-affinity binding is saturable (half-saturation at 4 nM) and shows definite regional and subcellular differences. The highest binding relative to protein content occurs in the striatum regionally and in microsomal fractions subcellularly. The subcellular distribution data also suggest that the d-LSD acceptor substance need not be confined to the neuronal soma or terminal membrane. The effects of related hallucinogens, neurotransmitters, serotonin (5-HT) and dopamine antagonists, and other drugs were studied to help determine whether central 5-HT receptors are identical with a site of LSD binding. Of the drugs tested, methiothepin was most effective in blocking the high-affinity, stereospecific binding of d-LSD. The pattern of drug effects suggests that the high-affinity, stereospecific binding site on brain membranes may not be identical with a 5-HT or dopamine receptor, but that LSD and nonpsychotomimetic congeners can bind to such receptors while simultaneously binding to one or more other points on the membrane in the immediate vicinity of the receptor. This is consistent with the view that LSD can act either agonistically or antagonistically at central 5-HT, and possibly dopamine, receptors in vivo.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 7
- Antagonism of histamine-activated adenylate cyclase in brain by D-lysergic acid diethylamide. Proceedings of the National Academy of Sciences December 1, 1977
- High-affinity 3H-serotonin binding to caudate: inhibition by hallucinogens and serotoninergic drugs. Psychopharmacology September 15, 1978
- Serotonin autoreceptors on dorsal raphe neurons: structure-activity relationships of tryptamine analogs Journal of Neuroscience October 1, 1981
- 1H Nuclear Magnetic Resonance: A Future Approach to the Metabolic Profiling of Psychedelics in Human Biofluids? Frontiers in Psychiatry 2021
- Hallucinogenic drug research--if so, so what? Symposium summary and commentary. Pharmacology, Biochemistry, and Behavior February 1986
and 2 more in the library