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N 1‐Methyl‐2‐ 125 I‐Lysergic Acid Diethylamide, a Preferred Ligand for In Vitro and In Vivo Characterization of Serotonin Receptors
Author(s) -
Hoffman Beth J.,
Scheffel Ursula,
Lever John R.,
Karpa Michael D.,
Hartig Paul R.
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb13135.x
Subject(s) - serotonin , receptor , lysergic acid diethylamide , chemistry , 5 ht receptor , dissociation constant , 5 ht2 receptor , radioligand , in vivo , serotonergic , ligand (biochemistry) , binding site , biochemistry , stereochemistry , biophysics , medicine , biology , microbiology and biotechnology
Methylation of 2‐ 125 I‐lysergic acid diethylamide ( 125 I‐LSD) at the N 1 position produces a new derivative, N 1‐methyl‐2‐ 125 I‐lysergic acid diethylamide ( 125 I‐MIL), with improved selectivity and higher affinity for serotonin 5‐HT 2 receptors. In rat frontal cortex homogenates, specific binding of 125 I‐MIL represents 80–90% of total binding, and the apparent dissociation constant ( K D ) for serotonin 5‐HT 2 receptors is 0.14 n M (using 2 mg of tissue/ml). 125 I‐MIL also displays a high affinity for serotonin 5‐HT 1C receptors, with an apparent dissociation constant of 0.41 n M at this site. 125 I‐MIL exhibits at least 60‐fold higher affinity for serotonin 5‐HT 2 receptors than for other classes of neurotransmitter receptors, with the dopamine D 2 receptor as its most potent secondary binding site. Studies of the association and dissociation kinetics of 125 I‐MIL reveal a strong temperature dependence, with very slow association and dissociation rates at 0°C. Autoradiographic experiments confirm the improved specificity of 125 I‐MIL. Selective labeling of serotonin receptors was observed in all brain areas examined. In vivo binding studies in mice indicate that 125 I‐MIL is the best serotonin receptor label yet described, with the highest frontal cortex to cerebellum ratio of any serotonergic radioligand. 125 I‐MIL is a promising ligand for both in vitro and in vivo labeling of serotonin receptors in the mammalian brain.