Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives
Andrew J. Hoffman, David E. Nichols
Journal of Medicinal Chemistry September 1, 1985 DOI: 10.1021/jm00147a022 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug discrimination assay Peer reviewed |
|---|---|
| Population | Rats trained to discriminate injections of d-LSD tartrate from saline |
| Interventions | N(6)-alkyl norlysergic acid N N-diethylamide derivatives |
| Dose | 185.5 nmol/kg |
| Topics | LSD |
| Keywords | Alkyl Stimulus control Discriminative model Stereochemistry |
| Citations | 44 |
| Key points | N(6)-ethyl and -allyl derivatives were 2–3 times more potent than LSD, while n-butyl was 10 times less potent, and no generalization occurred for norlysergic acid N,N-diethylamide or the N(6)-2-phenethyl derivative. |
Abstract
A convenient method for the synthesis of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives was developed. A series of these compounds was synthesized and tested for substitution in the two-lever drug discrimination assay, in rats trained to discriminate injections of d-LSD tartrate (185.5 nmol/kg, ip) from saline. A dose-response curve for each of the compounds in the series was generated. Structure-activity relationships were developed, based on comparison of the estimated ED50 values from these curves. Of the compounds that substituted for LSD, the N(6)-ethyl and -allyl were approximately 2-3 times more potent than LSD itself. The N(6)-propyl was equipotent to LSD, while the isopropyl derivative was half as active. The n-butyl compound was 1 order of magnitude less potent than LSD, suggesting a similarity to the SAR of certain serotonin and dopamine agonists. By contrast, no generalization occurred to norlysergic acid N,N-diethylamide and the N(6)-2-phenethyl derivative.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 26
- The Pharmacology of Lysergic Acid Diethylamide: A Review CNS Neuroscience & Therapeutics November 11, 2008
- Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology May 1, 2020
- Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD) ACS Chemical Neuroscience February 20, 2018
- Structure–activity relationships of serotonin 5‐HT2Aagonists Wiley Interdisciplinary Reviews Membrane Transport and Signalling February 28, 2012
- Return of the lysergamides. Part I: Analytical and behavioural characterization of 1‐propionyl‐d‐lysergic acid diethylamide (1P‐LSD) Drug Testing and Analysis October 12, 2015
and 21 more in the library