Cerebral and peripheral demethylation of psychotomimetics measured by expired 14CO2.
Demethylation of psychotomimetic compounds was measured by labeling each methyl and methoxy substitutent separately with 14C and injecting it into rats, intravenously and intracerebrally. Expired [14C]CO2 was measured continuously and the resultant multi-exponential curves yielded rates and integral demethylation. 5-Methoxy-N,N-dimethyltryptamine was not demethylated, eliminating one proposed metabolic pathway. 2,4,5-Trimethoxyphenalkylamines were demethylated less in the brain than peripherally, markedly so at the p-methoxy position, suggesting a possible biochemical site for endogenous induction of psychosis.
Sargent
T
T
Biomedical Division, Lawrence Berkeley Laboratory, University of California, Berkeley, CA 94720.
Braun
U
U
Braun
G
G
Kusubov
N
N
Bristol
K S
KS
D000662:Amphetamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D002245:Carbon Dioxide / Q000032:analysis*; D002250:Carbon Radioisotopes / Q000032:analysis; D006213:Hallucinogens / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007267:Injections; D007275:Injections, Intravenous; D008732:Methoxydimethyltryptamines / Q000493:pharmacokinetics*; D008745:Methylation; D015394:Molecular Structure; D010627:Phenethylamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000493:pharmacokinetics*
D000662:Amphetamines; D002250:Carbon Radioisotopes; D006213:Hallucinogens; D008732:Methoxydimethyltryptamines; D010627:Phenethylamines; D011985:Receptors, Serotonin; D014363:Tryptamines; C013344:2,4,5-trimethoxyphenylisopropylamine; D002245:Carbon Dioxide; C059578:2,4,5-trimethoxyphenethylamine