THE DISTRIBUTION AND METABOLISM OF LYSERGIC ACID DIETHYLAMIDE

Abstract

A specific and sensitive method for the estimation of LSD in biological material is described. After administration of LSD to the cat, the drug is found in all tissues in the following order of decreasing concentration: bile, plasma, lung, liver, kidney, brain, intestine, spleen cerebrospinal fluid, muscle, and fat. The drug is extensively bound to plasma proteins, and there is no hindrance in the passage of the drug across the blood-brain barrier. LSD is almost completely metabolized in the body, only negligible amounts of the drug being excreted in the urine or the stools. The liver is the major site of its metabolism. There are considerable species differences in the rate of biotransformation of LSD. LSD is transformed to 2-oxyLSD by an enzyme system present in liver micro-somes that requires O2 and a reduced-triphosphopyridine nucleotide generating system. The new compound, 2-oxyLSD, does not possess LSD-like activity in the central nervous system. Chlorpromazine (1 x 10-4 [image]) and [beta]-diethylaminoethyldiphenylpropyl acetate (SKF 525) (1 x 10-4 [image]) markedly inhibit the in vitro metabolism of LSD, while serotonin (1 x 10-3[image]) and reserpine (1 x 10-3M) inhibit the in vitro metabolism moderately.