As the 4-alkyl chain length is increased from shorter homologues such as DOM, DOET and DOPR which are all potent hallucinogens, the 5-HT2 binding affinity increases, rising to a maximum with the 4-(n-hexyl) derivative before falling again with even longer chains, but compounds with chain length longer than n-propyl, or with other bulky groups such as isopropyl, t-butyl or γ-phenylpropyl at the 4- position, fail to substitute for hallucinogens in animals or produce hallucinogenic effects in humans, suggesting these have low efficacy and are thus antagonists or partial agonists at the 5-HT2A receptor.
As the length of the 4-alkyl chain increases from shorter homologues such as DOM, DOET, and DOPR—potent hallucinogens—the affinity for binding to the 5-HT2 receptor rises. It peaks with the 4-(n-hexyl) derivative but then declines with longer chains. Compounds with a chain length beyond n-propyl or containing bulky groups like isopropyl, t-butyl, or γ-phenylpropyl at the 4-position do not substitute for hallucinogens in animals or produce hallucinogenic effects in humans, suggesting low efficacy and indicating they are antagonists or partial agonists at the 5-HT2A receptor.