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Lee E Schechter

Publications and source records attributed to Lee E Schechter.

22 records · Page 2Linked to original sources
PubMed2004

Studying rat brain neurochemistry using nanoprobe NMR spectroscopy: a metabonomics approach.

In the present experiments, in vivo microdialysis techniques together with nanoprobe NMR spectroscopy were used to evaluate the neurochemical environment of the rat frontal cortex. Metabonomics techniques of data reduction and pattern recognition were used to examine whether collected neurochemicals were sensitive to tetrodotoxin (TTX), a neurotoxin that when infused into discrete brain regions can help distinguish between the neuronal versus glial origin of neurochemicals in cerebrospinal fluid microdialysate. (1)H NMR spectra recorded on samples collected from the rat frontal cortex before and after an intracortical TTX infusion (10 microM for 60 min) were subjected to multivariate statistical analysis. Glutamate, isoleucine, valine, alanine, and alpha- and beta-hydroxybutyrate were found to have decreased concentrations after the addition of TTX, suggesting that their release is likely from cortical neurons. In contrast, lactate, formate, acetate, glucose, creatinine, pyruvate, and other neurochemicals remained unchanged following local application of TTX. The present findings extend our previous work combining the analytical technology of small-volume nanoprobe NMR spectroscopy with in vivo microdialysis in freely moving animals and show that it is possible to apply metabonomics methodology to this important class of biofluid to monitor changes in neurochemical composition of the rat brain.

Anesthetics, Local↗
PubMed2004

Studies toward the discovery of the next generation of antidepressants. 3. Dual 5-HT1A and serotonin transporter affinity within a class of N-aryloxyethylindolylalkylamines.

N-aryloxylethylindolealkylamines (5) having dual 5-HT transporter and 5-HT(1A) affinity are described. These compounds represent truncated analogues of our previously reported piperidinyl derivatives (3). Compounds in this investigation were found to have more similar affinities and functional activities for the 5-HT(1A) receptor and 5-HT transporter. Though 5-HT(1A) antagonism is not consistently observed throughout series 5, several molecular features were found to be essential to obtain high and balanced activities. The proper placement of a heteroatom in the aryl ring and the length of the linkage used to tether the indole moiety had significant influence on 5-HT(1A) and 5-HT transporter affinities. Introduction of a halogen into the aryl ring usually lowered intrinsic activity and in some cases led to full 5-HT(1A) antagonists. Compounds 33 and 34 were observed to be full 5-HT(1A) antagonists with K(i) values of approximately 30 nM for the 5-HT(1A) receptor and K(i) values of 5 and 0.5 nM for the 5-HT transporter, respectively. Unfortunately, similar to our previous series (3), compounds in this report also had high affinity for the alpha(1) receptor.

Amines↗
PubMed2004

Nanoprobe NMR spectroscopy and in vivo microdialysis: new analytical methods to study brain neurochemistry.

Nuclear magnetic resonance (NMR) spectroscopy was used to study the chemical composition of cerebrospinal fluid (CSF) microdialysate from the rat brain. In vivo microdialysis techniques were used in several brain regions including the frontal cortex, amygdala, striatum, nucleus accumbens and third ventricle and dialysate samples (20microl) were subsequently analyzed by one and two-dimensional 1H NMR experiments using a Varian nanoprobe. Neurochemical resonances were assigned on the basis of published chemical shifts [Lindon et al., Ann. Rep. NMR Spectrosc. 38 (1999) 1-88], correlation experiments and addition of standard compounds. Glucose, lactate, formate, pyruvate, creatinine, gamma-hydroxybutyrate, acetate, glutamate, glycine, tyrosine, isoleucine, leucine, alanine and choline were some of the neurochemicals unambiguously assigned. Additional studies in the frontal cortex showed that amino acids such as glutamate, alanine and isoleucine were sensitive to local tetrodotoxin (TTX) infusion. The NMR spectra were also subjected to multivariate statistical methods to compare the different brain regions examined. To our knowledge, the present experiments are the first to describe the combination of nanoprobe NMR technology with in vivo microdialysis for the analysis of brain neurochemistry in freely-moving rats.

Animals↗