8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, a potent and selective simplified ergot congener with central 5-HT-receptor stimulating activity
S. Hjorth, A. Carlsson, P. Lindberg, D. Sanchez, H. Wikström, L. -E. Arvidsson, U. Hacksell, J. L. G. Nilsson
Journal of Neural Transmission September 1, 1982 DOI: 10.1007/bf01276574 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats (implied by typical central nervous system pharmacology studies of this era) |
| Intervention | 8-OH-DPAT |
| Topics | Serotonin |
| Keywords | 8-hydroxy-2-di-n-propylaminotetralin Ergot congen |
| Key findings | 8-OH-DPAT is a potent and selective centrally acting 5-HT agonist, lacking effects on catecholamine receptors, and its effects are resistant to monoamine depletion. |
Abstract
It was demonstrated that the simplified ergot congener 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, is able to elicit pronounced biochemical and behavioural alterations indicative of central serotoninomimetic activity. Since these effects are resistant to prior monoamine depletion and/or synthesis inhibition by means of reserpine and α -propyldopacetamide (H22/54), respectively, they are most likely to be attributable to direct serotonin-receptor agonism by 8-OH-DPAT. With regard to central 5-HT neurotransmission the effects of 8-OH-DPAT-increased 5-HT levels, decreased 5-HIAA levels, 5-HT-synthesis rate and 5-HT utilization and inhibited 5-HT neuronal firing-are virtually identical, and comparable in potency, to those reported to result from the administration of lisuride or LSD. In contrast, however, to lisuride and LSD (included for comparative purposes in this study) as well as to several differently N-substituted, 5,6-dihydroxy, 6,7-dihydroxy and 5-, 6- and 7-monohydroxy 2-aminotetralins, 8-OH-DPAT lacks appreciable effects on central catecholamine receptors. The compound may thus be regarded the most potent, selective centrally acting 5-HT agonist described to date. accordance with this it was shown that the full-blown 5-HT-like behaviour syndrome induced by 8-OH-DPAT cannot be antagonized by reserpin phenoxybenzamine, propranolol and haloperidol. In addition, of the truputative 5-HT-receptor blockers cyproheptadine, methergoline and methrothepin only the latter was able to counteract the 8-OH-DPAT-induce syndrome. The results are discussed in relation to the recent subclassification of central 5-HT receptor sites. A comparison between the chemical structures and biological activities for different fragments of the ergot nucleus was also made. The data suggest, in that while the role of the A ring in the ergot structure for dopaminer activity at present is unclear, this ring may be important for the 5-HT-receptor activity like in e.g. lisuride and LSD. Moreover, based on the present results and literature reports, it is speculated that a selective 5-HT-receptor agonist such as 8-OH-DPAT would be liable to induce hallucinations in man.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
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| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 17
- Differential effects of 5-hydroxytryptamine1a selective drugs on the 5-HT behavioral syndrome. Pharmacology, Biochemistry, and Behavior June 1, 1986
- Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat European Journal of Pharmacology October 1, 1985
- The effects of 8-hydroxy-2-(di-n-propylamino)tetralin and other serotonergic agonists on performance in a radial maze: a possible role for 5-HT1A receptors in memory. Pharmacology, Biochemistry, and Behavior August 1, 1987
- Neuropharmacological reassessment of the discriminative stimulus properties ofd-lysergic acid diethylamide (LSD) Psychopharmacology 1987
- An in vivo dialysis and behavioural study of the release of 5-HT by p-chloroamphetamine in reserpine-treated rats. British Journal of Pharmacology May 1, 1989
and 12 more in the library
Cites 3
- Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide British Journal of Pharmacology September 1, 1968
- A new view of the structural relationship between LSD and mescaline Brain Research Bulletin May 1, 1977
- Effects of LSD-25 on brain serotonin. Journal of Pharmacology and Experimental Therapeutics November 1, 1961