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Synthesis and 5‐HT 2A Radioligand Receptor Binding Assays of DOMCl and DOMOM, Two Novel 5‐HT 2A Receptor Ligands
Author(s) -
Harms Antje,
Ulmer Ernst,
Kovar KarlArtur
Publication year - 2003
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200390014
Subject(s) - radioligand , chemistry , radioligand assay , receptor , affinities , stereochemistry , chemical synthesis , 5 ht receptor , hallucinogen , pharmacology , serotonin , biochemistry , in vitro , biology
A synthesis of two new active substances, DOMCl (1‐(4‐chloromethyl‐2, 5‐dimethoxyphenyl)‐2‐propanamine; 2 ) and DOMOM (1‐(2, 5‐dimethoxy‐4‐methoxymethylphenyl)‐2‐propanamine; 3 ), was developed. Unexpectedly, the Blanc reaction permitted successful synthesis of 2, 5‐dimethoxyphenylpropylamine derivatives having a substituted methyl group in position 4 since solvation of the reactant occurs during the reaction. Afterwards, their affinities towards the 5‐HT 2A receptor were examined in 5‐HT 2A radioligand receptor binding assays. The study of these substances is of considerable interest because they were predicted, by preliminary molecular modeling studies based on mescalin units, to be potential new hallucinogens that should be added to the list of substances prohibited by law. It was assumed that DOMCl would be 82 times more potent as a hallucinogen than mescalin, and DOMOM would be 94 times more potent. The 5‐HT 2A radioligand receptor binding studies showed that the affinities of DOMCl and DOMOM for the 5‐HT 2A receptor are less than expected but are nevertheless 1.6 and 8.7 times higher, respectively, than that of mescalin. Therefore, scheduling these substances as potential drugs of abuse might be considered.