The 5-fluoro comopounds are more active than the 6-subtitiuted derivatives in inducing spontaneous locomotion when administered to reserpinized white mice. Both 6-F-DET and DET exerted peripheral activity when tested in humans, but only the fluorine-free compound seemed to bear hallucinogenic qualitities. These reults may be explained by change in the metabolic pathway of the tryptamine substituted at the 6-position in the indole nucleus.
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5-F-AMT and 6-F-AMT were tested on mice using reserpine-induced ptosis reversal and activity cage tests. In these tests, 5-F-AMT acted like the parent compound (AMT) but there was a marked decrease in activity especially in the locomotor test with the 6-fluoro derivative.
The effect of 6-F-DET was compared with DET in six patients and one normal volunteer. Both drugs were given intramuscularly in 1mg/kg doses. DET produced sympathomimetic autonomic symptoms, perceptual disturbances, hallucinations, mood changes, and difficulaties thinking and speaking. 6-F-DET in the same persons produced the autonomic symptoms and mood changes without the perceptual and thinking disturbances characteristic of hallucinogenic drugs.
in the urine of patients treated with DET, various amounts of 6-HO-DET could be found (4.5 to 20.3% of administered DET dose). In the case of the 6-fluoro analog the urine instead contained large amounts of unchanged 6-F-DET and no detectable 6-HO-DET.
These reults indicate that the 6-fluoro substitution of the indole ring may represent an important structural change resulting in a different metabolic pathway, and quite possibly in a different physical and pharmacological action of the compound.
