James R. Epperson

Indanyl piperazines as melatonergic MT2 selective agents

Optimization of a benzyl piperazine pharmacophore produced N-acyl-4-indanyl-piperazines that bind with high affinity to melatonergic MT(2) receptors. (R)-4-(2,3-dihydro-6-methoxy-1H-inden-1-yl)-N-ethyl-1-piperazine-carboxamide fumarate (13) is a water soluble, selective MT(2) agonist, which produces advances in circadian phase in rats at doses of 1-56 mg/kg that are no different from those of melatonin at 1 mg/kg. Unlike melatonin, 13 produced only weak contractile effects in rat tail artery.

Synthesis and excitatory amino acid pharmacology of some novel quinoxalinediones

Abstract The synthesis and amino acid pharmacology of twelve N-substituted quinoxalinediones is reported. In particular, compounds 4a and 4b show significant antagonism at both the AMPA and glycine-site NMDA receptors. The functional antagonism of 4a has been demonstrated.

Conformationally restricted homotryptamines. Part 6: Indole-5-cycloalkyl methylamines as selective serotonin reuptake inhibitors

Racemic 5-(trans-2-aminomethylcyclopropyl)indoles, 5-(trans-2-aminomethylcyclopentyl) indoles, and 5-(cis-2-aminomethylcyclopentyl)indoles were synthesized and evaluated as selective serotonin reuptake inhibitors. These analogs followed SAR trends similar to those previously reported for 3-cycloalkyl substituted indoles. The most potent analogs exhibited single digit nanomolar inhibition at the human serotonin transporter but were 10-fold less active than the previously reported compounds.

Chapter 5. Pharmacological Interventions in the Sleep Process

Publisher Summary This chapter analyzes the pharmacologlcal interventions in the sleep process. Insomnia is the term used to describe difficulties in initiating sleep, maintaining sleep, or obtaining a restorative sleep. It is a symptom that can arise for a multitude of reasons and represents a significant public health problem. About 40% of the individuals suffering from insomnia attempt to self-medicate with over-the-counter agents or alcohol, indicating that a clear need still exists for accepted, effective medications. Because the likelihood of severe or chronic insomnia increases with age, the management of insomnia in the geriatric population is also a significant concern. The benzodiazepines (BZs) remain the mainstay of hypnotic therapy. The BZs produce their effects by acting at benzodiazepine receptors (BZRs) that are allosteric modulatory sites of the GABA A receptor. The chapter overviews current research aimed at improved pharmacological intervention in the sleep process and discusses the concepts related to GABA A benzodiazepine receptor ligands and melatonin receptor ligands. Aenosine receptor ligands are described and an overview of histamine receptor ligands is also presented.