Binding to the serotonin 5-HT2 receptor by the enantiomers of 125I-DOI.
Preliminary receptor binding experiments with the stereoisomers of 125I-DOI, a new putative 5-HT2 agonist ligand, were conducted. The results indicated specific binding for both enantiomers, with a two-site model giving the best fit to the binding data. R-125I-DOI showed a high affinity dissociation constant of 1.26 nanoMolar, while the less active S-enantiomer had a two-fold lower affinity. Competition experiments with several 5-HT2 agonists also indicated a two site model, with high affinity inhibition constants less than 10 nanoMolar. These results show a stereoselective effect of ligand binding to the 5-HT2 receptor. The use of this ligand to investigate agonist-receptor interactions could be instrumental in the elucidation of the role of serotonergic systems in the mechanism of action of hallucinogens.
Johnson
M P
MP
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
Hoffman
A J
AJ
Nichols
D E
DE
Mathis
C A
CA
D000662:Amphetamines / Q000378:metabolism*; D000818:Animals; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D013237:Stereoisomerism
D000662:Amphetamines; D007457:Iodine Radioisotopes; D011985:Receptors, Serotonin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine