Lysergic acid 2-butyl amide
Encyclopedia
Lysergic acid 2-butyl amide (2-Butyllysergamide, LSB) is an analogue of LSD
originally developed by Richard Pioch at Eli Lilly
in the 1950s, but mostly publicised through research conducted by the team led by David E. Nichols
at Purdue University
. It is a structural isomer of LSD, with the two ethyl groups on the amide nitrogen having been replaced by a single butyl group, joined at the 2-position. It is one of the few lysergamide derivatives to exceed the potency of LSD in animal drug discrimination assays, with the (R) isomer having an ED50 of 33nmol/kg for producing drug-appropriate responding, vs 48nmol/kg for LSD itself. The corresponding (R)-2-pentyl analogue has higher binding affinity
for the 5-HT1A and 5-HT2A receptors, but is less potent in producing drug-appropriate responding, suggesting that the butyl compound has a higher efficacy
at the receptor target. The drug discrimination assay for LSD in rats involves both 5-HT1A
and 5-HT2A mediated components, and while lysergic acid 2-butyl amide is more potent than LSD as a 5-HT1A agonist, it is slightly less potent as a 5-HT2A agonist, and so would probably be slightly less potent than LSD as a hallucinogen in humans. The main use for this drug has been in studies of the binding site at the 5-HT2A receptor
through which LSD exerts most of its pharmacological effects, with the stereoselective activity of these unsymmetric monoalkyl lysergamides foreshadowing the subsequent development of compounds such as Lysergic acid 2,4-dimethylazetidide
.
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...
originally developed by Richard Pioch at Eli Lilly
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
in the 1950s, but mostly publicised through research conducted by the team led by David E. Nichols
David E. Nichols
David E. Nichols is an American pharmacologist and medicinal chemist.Presently the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology at Purdue University, Nichols has worked in the field of psychoactive drugs since 1969...
at Purdue University
Purdue University
Purdue University, located in West Lafayette, Indiana, U.S., is the flagship university of the six-campus Purdue University system. Purdue was founded on May 6, 1869, as a land-grant university when the Indiana General Assembly, taking advantage of the Morrill Act, accepted a donation of land and...
. It is a structural isomer of LSD, with the two ethyl groups on the amide nitrogen having been replaced by a single butyl group, joined at the 2-position. It is one of the few lysergamide derivatives to exceed the potency of LSD in animal drug discrimination assays, with the (R) isomer having an ED50 of 33nmol/kg for producing drug-appropriate responding, vs 48nmol/kg for LSD itself. The corresponding (R)-2-pentyl analogue has higher binding affinity
Dissociation constant
In chemistry, biochemistry, and pharmacology, a dissociation constant is a specific type of equilibrium constant that measures the propensity of a larger object to separate reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt splits up into...
for the 5-HT1A and 5-HT2A receptors, but is less potent in producing drug-appropriate responding, suggesting that the butyl compound has a higher efficacy
Intrinsic activity
Intrinsic activity or efficacy refers to the relative ability of a drug-receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its molecular target, and the EC50, which is a measure of the...
at the receptor target. The drug discrimination assay for LSD in rats involves both 5-HT1A
5-HT1A receptor
The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...
and 5-HT2A mediated components, and while lysergic acid 2-butyl amide is more potent than LSD as a 5-HT1A agonist, it is slightly less potent as a 5-HT2A agonist, and so would probably be slightly less potent than LSD as a hallucinogen in humans. The main use for this drug has been in studies of the binding site at the 5-HT2A receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
through which LSD exerts most of its pharmacological effects, with the stereoselective activity of these unsymmetric monoalkyl lysergamides foreshadowing the subsequent development of compounds such as Lysergic acid 2,4-dimethylazetidide
Lysergic acid 2,4-dimethylazetidide
Lysergic acid 2,4-dimethylazetidide is an analogue of LSD developed by the team led by David E. Nichols at Purdue University. It was developed as a rigid analogue of LSD with the diethylamide group constrained into an azetidine ring in order to map the binding site at the 5-HT2A receptor...
.