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.
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
M P
MP
Johnson
A J
AJ
Hoffman
D E
DE
Nichols
C A
CA
Mathis
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