Prevention of drug-induced memory impairment by immunopharmacotherapy.

Abstract

One approach to treating drug abuse uses antidrug antibodies to immunize subjects against the illicit substance rather than administering therapeutics that target the specific CNS site of action. At present, passive vaccination has recognized efficacy in treating certain gross symptoms of drug misuse, namely, motor activation, self-administration, and overdose. However, the potential for antibodies to prevent drug-induced changes involving finer cognitive processes, such as benzodiazepine-associated amnesia, remains unexplored. To address this concept, a flunitrazepam hapten was synthesized and employed in the generation of a panel of high affinity monoclonal antibodies. Anti-flunitrazepam mAb RCA3A3 ( K d,app = 200 nM) was tested in a mouse model of passive immunization and subsequent mole-equivalent challenge with flunitrazepam. Not only was flunitrazepam-induced sedation prevented but immunization also conferred protection to memory consolidation as assessed through contextual and cued fear conditioning paradigms. These results provide evidence that immunopharmacotherapeutic blockade of drug intoxication also preserves complex cognitive function.

• Authors: Jennifer B Treweek, Chengzao Sun, Alexander V Mayorov, Longwu Qi, Coree L Levy, Amanda J Roberts, Tobin J Dickerson, Kim D Janda
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 51 Issue 21 Pg. 6866-75 (Nov 13 2008) ISSN: 1520-4804 [Electronic] United States
• PMID: 18921991 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Monoclonal
• Flunitrazepam

Topics

• Animals
• Antibodies, Monoclonal (immunology, therapeutic use)
• Female
• Flunitrazepam (immunology)
• Immunotherapy
• Locomotion (drug effects)
• Memory Disorders (chemically induced, immunology, prevention & control)
• Mice
• Molecular Structure