Chunrong Ma
University of Wisconsin–Milwaukee
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Featured researches published by Chunrong Ma.
Neuropsychopharmacology | 2003
Harry L. June; Katrina L. Foster; Peter F. McKay; Regat Seyoum; James E. Woods; Scott C. Harvey; William J.A. Eiler; Collette Grey; Michelle R. Carroll; Shannan McCane; Cecily M. Jones; Wenyuan Yin; Dynesha Mason; Rancia Cummings; Marin Garcia; Chunrong Ma; Pullela V. Sarma; James M. Cook; Phil Skolnick
It has been hypothesized that alcohol addiction is mediated, at least in part, by specific γ-aminobutyric acidA (GABAA) receptors within the ventral pallidum (VP). Among the potential GABAA receptor isoforms regulating alcohol-seeking behaviors within the VP, the GABAA α1 receptor subtype (GABAA1) appears pre-eminent. In the present study, we developed β-carboline-3-carboxylate-t-butyl ester (βCCt), a mixed agonist–antagonist benzodiazepine (BDZ) site ligand, with binding selectivity at the A1 receptor to explore the functional role of VPA1 receptors in the euphoric properties of alcohol. The in vivo actions of βCCt were then determined following microinfusion into the VP, a novel alcohol reward substrate that primarily expresses the A1 receptor. In two selectively bred rodent models of chronic alcohol drinking (HAD-1, P rats), bilateral microinfusion of βCCt (0.5–40 μg) produced marked reductions in alcohol-reinforced behaviors. Further, VP infusions of βCCt exhibited both neuroanatomical and reinforcer specificity. Thus, no effects on alcohol-reinforced behaviors were observed following infusion in the nucleus accumbens (NACC)/caudate putamen (CPu), or on response maintained by saccharin. Parenteral-administered βCCt (1–40 mg/kg) was equally effective and selective in reducing alcohol-reinforced behaviors in P and HAD-1 rats. Additional tests of locomotor activity revealed that βCCt reversed the locomotor sedation produced by both chlordiazepoxide (10 mg/kg) and EtOH (1.25 g/kg), but was devoid of intrinsic effects when given alone. Studies in recombinant receptors expressed in Xenopus oocytes revealed that βCCt acted as a low-efficacy partial agonist at α3β3γ2 and α4β3γ2 receptors and as a low-efficacy inverse agonist at α1β3γ2, α2β3γ2, and α5β3γ2 receptors. The present study indicates that βCCt is capable of antagonizing the reinforcing and the sedative properties of alcohol. These anti-alcohol properties of βCCt are primarily mediated via the GABAA1 receptor. βCCt may represent a prototype of a pharmacotherapeutic agent to effectively reduce alcohol drinking behavior in human alcoholics.
Psychopharmacology | 2002
Donna M. Platt; James K. Rowlett; Roger D. Spealman; James M. Cook; Chunrong Ma
Abstract Rationale. Delineation of the receptor mechanisms underlying the behavioral effects of benzodiazepines should allow for the development of drugs with improved clinical utility and reduced side effects. Objectives. The purpose of the present study was to investigate the role of GABAA/α1 receptors in the sedative and motor-impairing effects of benzodiazepines. Methods. Squirrel monkeys were tested with the GABAA/α1-preferring agonist zolpidem and the nonselective benzodiazepine agonist triazolam alone and in combination with the GABAA/α1-preferring antagonist β-CCt and the nonselective benzodiazepine antagonist flumazenil. During 30-min experimental sessions, all occurrences of normal behaviors like locomotion, environment- and self-directed behaviors, as well as side effects such as ataxia, rest and procumbent postures were scored. Results. Zolpidem and triazolam produced dose-dependent reductions in locomotion and environment-directed behavior and increased ataxia and procumbent posture. Triazolam, but not zolpidem, also engendered species-typical rest posture at some doses. Flumazenil antagonized all of the behavioral effects of zolpidem and triazolam, whereas β-CCt antagonized only zolpidem- and triazolam-induced ataxia. Conclusions. GABAA/α1 receptor mechanisms appear to play a key role in the ataxic effects of benzodiazepine agonists in squirrel monkeys, similar to recent results with transgenic mice. In contrast to the findings of these recent studies, GABAA mechanisms other than or in addition to those mediated at the α1 subunit may play a more important role in the sedative/hypnotic effects of benzodiazepines in squirrel monkeys.
Tetrahedron Letters | 2000
Xiaoxiang Liu; Tao Wang; Qingge Xu; Chunrong Ma; James M. Cook
Abstract The enantiomer of affinisine has been synthesized (from l -tryptophan) with 100% diastereoselectivity via the asymmetric Pictet–Spengler reaction coupled with a Pd 0 (enolate mediated) coupling process. This enantiomer has also been converted into a key intermediate which provides a route to the enantiomers of both macroline and alstonerine following the previous work of LeQuesne.
Tetrahedron Letters | 1999
Chunrong Ma; Xiaoxiang Liu; Shu Yu; Shuo Zhao; James M. Cook
A concise synthesis of optically active trytophan derivatives was developed via diastereoselective alkylation of the Schollkopf chiral auxiliary 4 to provide alkyne 2 which underwent palladium-catalyzed heteroannulation with iodoanilines 1 to furnish protected tryptophans 3. Hydrolysis and subsequent saponification of 3 provided the desired tryptophans 12 in good yields.
Tetrahedron Letters | 2000
Chunrong Ma; Shu Yu; Xiaohui He; Xiaoxiang Liu; James M. Cook
An efficient method has been developed via the Schollkopf chiral auxiliary for the asymmetric synthesis of the important tryptophan analogs: l-isotryptophan, l-benzo[f]tryptophan and l-homotryptophan.
Tetrahedron Letters | 1999
Chunrong Ma; Xiaohui He; Xiaoxiang Liu; Shu Yu; Shuo Zhao; James M. Cook
Tosylates, diphenylphosphates and bromides were employed to study the effect of the leaving group on the alkylation diastereoselectivity of the Schollkopf chiral auxiliary 1 at aliphatic, benzylic, propargylic and allylic electrophilic centers. The diastereoselectivity generally follows the pattern: diphenylphosphate > tosylate > bromide. In terms of both diastereoselectivity and yield, each leaving group possesses a different advantage.
Journal of Organic Chemistry | 2001
Chunrong Ma; Xiaoxiang Liu; Xiaoyan Li; Judith L. Flippen-Anderson; Shu Yu; James M. Cook
Journal of Medicinal Chemistry | 2000
Qi Huang; Xiaohui He; Chunrong Ma; Ruiyan Liu; Shu Yu; Charlotte A. Dayer; Galen R. Wenger; Ruth McKernan; James M. Cook
The Journal of Neuroscience | 2002
Scott C. Harvey; Katrina L. Foster; Pete F. McKay; Michelle R. Carroll; Regat Seyoum; James E. Woods; Collette Grey; Cecily M. Jones; Shannan McCane; Rancia Cummings; Dynesha Mason; Chunrong Ma; James M. Cook; Harry L. June
Journal of Medicinal Chemistry | 1998
Eric D. Cox; Hernando Diaz-Arauzo; Qi Huang; Mundla S. Reddy; Chunrong Ma; Brad Harris; Ruth McKernan; Phil Skolnick; James M. Cook