^abcPfaff RC, Huang X, Marona-Lewicka D, Oberlender R, Nichols DE (1994)."Lysergamides revisited".NIDA Research Monograph.146:52–73.PMID8742794.The other major area now being examined is substitution on the amide function. Most lysergamides that have been subjected to clinical studies were reported in the mid- to late-1950s. Table 2 lists relative potency in humans for most of the amides that were studied. The amides were not studied systematically, and their characterization in clinical studies was rudimentary. [...] TABLE 2. Relative human potency of lysergic acid amides* [...] It should be noted in table 2 that none of the compounds has more than about 30 percent of the activity of LSD. This is something that has always perplexed researchers in this field: What is it about the diethyl group that may be unique in this molecule? Even a substitution with the same number of carbon atoms, such as the N-methyl-N-propyl derivative, shows only about one-thirtieth the potency of LSD. The N-methyl-N-propyl presumably would have similar pharmacokinetics, with comparable amounts of the drug expected to enter the brain, and yet this compound is only weakly active. Even the N-methyl-N-ethyl has low activity compared with LSD. With the N,N-diethyl (LSD) one sees optimum activity, but the N-ethyl-N-propyl is back to about one-third the potency of LSD, and N,N-dipropyl is down to one-tenth.
^Hofmann A (June 1959)."Psychotomimetic drugs; chemical and pharmacological aspects"(PDF).Acta Physiologica et Pharmacologica Neerlandica.8:240–258.PMID13852489.Systematic variations of the substituents in the amide grouping has resulted in the synthesis of a great number of substances (STOLL and HOFMANN, 1955) which are listed in table 1. Pharmacological and clinical investigations of this group of compounds have not yet been concluded. None of these compounds shows the high specific psychic activity of LSD. The next higher and the next lower homologue of LSD, the lysergic acid dimethylamide and the dipropylamide, are about ten times less active on the psyche, but the vegetative effects are the same as that of the diethylamide. But there are some derivatives which have other interesting psychic effects, for example the monoethylamide and the unsubstituted amide show some sedative or even hypnotic effects. [...] TABLE 1 Variations in the acid amide group of the LSD molecule [...]
^Abramson HA, Rolo A (September 1965). "Lysergic acid diethylamide (LSD-25). 38. Comparison with action of methysergide and psilocybin on test subjects".The Journal of Asthma Research.3 (1):81–96.doi:10.3109/02770906509106904.PMID5318626.
^Valter K, Arrizabalaga P, Landry J (1998).Designer Drugs Directory. Elsevier Science. p. 79.ISBN978-0-08-053032-1. Retrieved9 March 2025.2.2 LSD Analogues Being extremely potent and relatively easy to produce, LSD (1, R1=R2=Et;) is a drug particularly suited for illicit traffic. Several procedures for its manufacture have been developed and mastered by clandestine chemists [1]. However, diethylamine, the key precursor in LSD synthesis is a highly suspect and closely controlled chemical and has been occasionally replaced by another suitable dialkylamine [2]. Consequently, in spite of their generally lower potency, several LSD analogues have sporadically been detected on the drug market. Thus, the ethylpropylamide (LEP-57; 1, R1=Et; R2=n-Pr) shows about 50% of LSD psychotomimetic activity in man. The morpholide (2) and the methylpropylamide (LMP-55, LAMPA; 1, R1=Me; R2=n-Pr) [7] are still less active (30% [3], 10-15 % [4,5], respectively). The identification of these substances was described in several recent papers [6].
