Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives.
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.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004193:Discrimination Learning / Q000187:drug effects*; D008238:Lysergic Acid Diethylamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D051381:Rats; D013329:Structure-Activity Relationship
D008238:Lysergic Acid Diethylamide