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Christian ST, CmClain LD, Morin RD, Benington F.
“Blockage of LSD Binding at its High Affinity Site on Synaptosomal Membranes by l-Methyl-1,2,5,6-Tetrahydropyridine-N,N-Diethyl- carboxamide”.
Experientia. 1975;31:910-911.
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Abstract
Smythies et al.(1) in an attempt to delineate the activity of hallucinogenic agents based on classical structure-activity relationships discovered a most interesting phaenomenon related to the compund 1-methyl-1,2,5,6-tetrahydropyridine-N,N-diethylcarbozamide (THPC). The structure of this compound as shown in Figure 1 indicateds its relationship to LSD through the D-ring of the LSD molecule. These investigators had postulated, on the basis of structure activity comparisons, that THPC in sufficiently high concentrations should, in fact, cross the blood brain barrier and act as a competitive antagonist of the hallucinatory activity of LSD. In order to test this hypothesis the modification of rodent behavior produced by LSD was quantified using Bovet-Gatti profiles on a Sidman avoidance schedule. Having established these profiles on rats given LSD the ability of THPC to block this behavior was tested by premedicating the rat with a dose of THPC equivalent to 15 mg/kg of the drug. The drug was given i.p. approximately 45 minutes before 0.1 mg/kg of LSD was given to the animal. Results of these studies clearly indicated that THPC brought about an almost complete abolition of the behavioral disruption produced by LSD intoxication. Since we have been working for some time inour laboratory characterizing the properties of the high affinity for LSD binding site on synaptosomal memberanes from rat brain, we were intrigued by the idea of obtaining molecular (rather than behavioral) evidence for the blockade of LSD binding by THPC.
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