While the idea of immunopharmacotherapy is not new, its application to the treatment of drug abuse has received much attention in recent years. In order to assess the efficacy of passive immunization against an abused drug, we will evaluate the ability of monoclonal antibodies (mAb's) raised against flunitrazepam to alleviate drug-induced psychomotor and cognitive impairments. Under a mouse model, we will employ locomotor activity and contextual learning assays to validate the ability of a mAb, selected for its high binding affinity to flunitrazepam, to sequester the drug and block its effect. The above results will be compared to a second set of experiments incorporating ethanol coadmistration with flunitrazepam. Assessing whether immunization still rescues impaired behavior adds relevancy to the study given that flunitrazepam is usually ingested in polydrug combinations. We have hypothesized that the mAb will rescue the impaired motor coordination and learning seen in flunitrazepam-treated mice, and in mice receiving flunitrazepam in conjunction with other CMS depressants. This study will validate a model for immunopharmacotherapy as well as test an immunization strategy relevant in polydrug overdose cases involving flunitrazepam. In addition to extending the field of immunopharmacotherapy, this project has direct implications into public health and well being. Flunitrazepam is widely used in facilitating sexual assault by impairing the victim's cognition and memory, and according to publications from NIDA and the DBA, coabused with heroin, cocaine, and alcohol. Given the number of documented sexual assault cases as well as fatalities associated with combining flunitrazepam and other CMS sedatives, further examination into the prevention of flunitrazepam intoxication and of polydrug models involving this potent benzodiazepine is justified. ? ? ?
|Treweek, Jennifer B; Janda, Kim D (2012) An antidote for acute cocaine toxicity. Mol Pharm 9:969-78|
|Treweek, Jennifer B; Roberts, Amanda J; Janda, Kim D (2011) Immunopharmacotherapeutic manifolds and modulation of cocaine overdose. Pharmacol Biochem Behav 98:474-84|
|Treweek, Jennifer B; Roberts, Amanda J; Janda, Kim D (2010) Superadditive effects of ethanol and flunitrazepam: implications of using immunopharmacotherapy as a therapeutic. Mol Pharm 7:2056-68|
|Treweek, Jennifer B; Dickerson, Tobin J; Janda, Kim D (2009) Drugs of abuse that mediate advanced glycation end product formation: a chemical link to disease pathology. Acc Chem Res 42:659-69|
|Treweek, Jennifer B; Sun, Chengzao; Mayorov, Alexander V et al. (2008) Prevention of drug-induced memory impairment by immunopharmacotherapy. J Med Chem 51:6866-75|