Receptor Profiles of Lysergamides related to LSD

Investigator: David E. Nichols, PhD
Purdue University – West Lafayette, IN
Contact: David E. Nicholas

Sponsor: Heffter, Promind
Laboratory research, no human or animal subjects. It is well known that the nature of the amide function of lysergamides is critical to conferring activity and high potency onto these molecules. The N,N-diethylamide (LSD) is unique among all the known amides, both for the qualitative aspects of its effects and for its extremely high potency. This project is evaluating a series of lysergamides of varying amide structure using radioligand competition studies at cloned human brain neurotransmitter receptors expressed in cell lines. The project seeks to identify in these data the possible reasons for the high degree of variability inactivity of the various amides. That is, is there a specific subset of receptors to which LSD binds that less potent lysergamides do not? In addition, intracellular signaling pathways are being examined to determine whether all lysergamides activate the same intracellular biochemical events.