The present application proposes research projects that will enhance the ability of our institution to conduct drug abuse research. The objectives of this proposal are: 1) To strengthen the institutional infrastructure to encourage and foster increased research activity in drug abuse, 2) To enhance the capability of faculty and staff to perform research to facilitate independent drug abuse research careers, and 3) To involve outstanding students in research in order to encourage them to pursue careers in drug abuse research. Four pilot projects and seven individual research subprojects are proposed. The pilot projects and individual research subprojects focus on analytical analysis and development of new drug products for disease states related to drugs of abuse. The three-dimensional structure and electronic character of cocaine analogs and dopamine transporter ligands will be determined, Slow release drug delivery systems will be developed for treating drug addictions. For example, a biodegradable microcapsules containing buprenorphine will be developed and evaluated for release characteristics. In addition, a biodegradable microcapsule drug delivery system releasing a catalytic antibody to cocaine will be evaluated and optimized for preventing the effects of cocaine in rodents. The in vivo and in vitro cannabinoid metabolism, using highly sensitive and specific analytical cocaine in rodents. The in vivo and in vitro cannabinoid metabolism, using highly sensitive and specific analytical methodology will be studied using high performance liquid chromatography coupled to a tandem mass spectrometer. The influence of nicotine and morphine on a rodent model of diabetes mellitus. The design, synthesis and in vivo evaluation of novel anionic chemical delivery conjugates of selected AIDS drugs and addiction treatment drugs to the brain will be investigated. Novel anti-Pneumocystis carinii drugs with not only less toxicity, but neuroprotective action, will be synthesized to enable improved drug therapy of stimulant-abusing AIDS patients. The limited equipment requested will not only enable the proposed research to be carried out, but will strengthen the institutional infrastructure. Finally, this revised continuation application will increase the number of outstanding students conducting drug abuse research.
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