N1‐Methyl‐2‐125I‐Lysergic Acid Diethylamide, a Preferred Ligand for In Vitro and In Vivo Characterization of Serotonin Receptors

Beth J. Hoffman, Ursula Scheffel, John R. Lever, Michael D. Karpa, Paul R. Hartig

Research output: Contribution to journalArticle

Abstract

Abstract: Methylation of 2‐125I‐lysergic acid diethylamide (125I‐LSD) at the N1 position produces a new derivative, N1‐methyl‐2‐125I‐lysergic acid diethylamide (125I‐MIL), with improved selectivity and higher affinity for serotonin 5‐HT2 receptors. In rat frontal cortex homogenates, specific binding of 125I‐MIL represents 80–90% of total binding, and the apparent dissociation constant (KD) for serotonin 5‐HT2 receptors is 0.14 nM (using 2 mg of tissue/ml). 125I‐MIL also displays a high affinity for serotonin 5‐HT1C receptors, with an apparent dissociation constant of 0.41 nM at this site. 125I‐MIL exhibits at least 60‐fold higher affinity for serotonin 5‐HT2 receptors than for other classes of neurotransmitter receptors, with the dopamine D2 receptor as its most potent secondary binding site. Studies of the association and dissociation kinetics of 125I‐MIL reveal a strong temperature dependence, with very slow association and dissociation rates at 0°C. Autoradiographic experiments confirm the improved specificity of 125I‐MIL. Selective labeling of serotonin receptors was observed in all brain areas examined. In vivo binding studies in mice indicate that 125I‐MIL is the best serotonin receptor label yet described, with the highest frontal cortex to cerebellum ratio of any serotonergic radioligand. 125I‐MIL is a promising ligand for both in vitro and in vivo labeling of serotonin receptors in the mammalian brain.

Original languageEnglish (US)
Pages (from-to)115-124
Number of pages10
JournalJournal of Neurochemistry
Volume48
Issue number1
DOIs
StatePublished - Jan 1987

Keywords

  • N1‐Methyl‐2‐I‐lysergic acid diethylamide—I‐Lysergic acid diethylamide—Serotonin 5‐HT receptor—Serotonin 5‐HT receptor—In vivo labeling

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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